Heading to the right: The effect of aperture width on navigation asymmetries for miniature remote-controlled vehicles.

Our ability to attend to the environment is asymmetrical and affects activities like navigation. This study investigated whether rightward deviations exist for miniaturized vehicles. Experiment 1 asked participants (n = 26) to navigate a remote-controlled car through apertures that were 200, 300 or 400 mm wide. Analyses revealed a nonsignificant trend for the rightward deviation to increase with aperture width. None of the deviations was significantly to the right. Experiment 2 (n = 16) elevated the car to eye level to control for upper/lower visual-field effects. The results were unchanged. Experiment 3 (n = 16) altered the car's mechanical drive to control veering effects, and the results were unchanged. Data from Experiments 1-3 were combined to increase statistical power and showed that the rightward deviation increased for wider apertures. Experiment 4 (n = 17) investigated deviations for wider apertures (1,100 mm) and found a rightward deviation. Finally, Experiment 5 (n = 24) used a different type of remote-controlled vehicle. A rightward deviation, which increased with width, was observed. In addition, the degree of rightward deviation was related to the perceived middle of the aperture. It appears that systematic rightward deviations occur for miniaturized vehicles, which increase with aperture width. The implications of these results for attentional explanations of rightward deviation are discussed. (PsycINFO Database Record

Involvement of the renin-angiotensin system in the development of nephrogenic systemic fibrosis-like lesions in the RenTag mouse model.

BACKGROUND: Renin-angiotensin system (RAS) activation increases angiotensin II production stimulating profibrotic factors, especially in the setting of chronic kidney disease. Nephrogenic systemic fibrosis (NSF) has been associated with gadolinium (Gd) exposure and renal failure. RAS involvement in NSF is unclear compared to transforming growth factor beta and Smad. RenTag mice were chosen to investigate the role of RAS in NSF-like dermal fibrosis because they demonstrated dermal fibrosis at birth, perturbations of RAS in subcutaneous tissue, and renal failure within 4 weeks of age. METHODS: Wild-type and RenTag mice were injected weekly with a supratherapeutic dose of intravenous gadodiamide (3.0 mmol/kg body weight) and killed at 12 weeks of age for skin and kidney histology. RESULTS: RenTag mice had elevated BUN levels, pitted kidneys, and glomerular damage. RenTag mice skin revealed an increased density of fibroblasts, no mucopolysaccharide deposits, and increased collagen fibril density regardless of Gd exposure. Skin and kidney histopathology of wild-type mice were normal regardless of Gd exposure. CD34 positivity was higher in RenTag compared to wild-type. CONCLUSIONS: Since RenTag dermal lesions remained unchanged after gadolinium exposure in the setting of renal failure, this animal model suggests perturbations of subcutaneous RAS may be involved in Gd-naïve dermal fibrosis.

Identification of renin progenitors in the mouse bone marrow that give rise to B-cell leukaemia.

The cell of origin and triggering events for leukaemia are mostly unknown. Here we show that the bone marrow contains a progenitor that expresses renin throughout development and possesses a B-lymphocyte pedigree. This cell requires RBP-J to differentiate. Deletion of RBP-J in these renin-expressing progenitors enriches the precursor B-cell gene programme and constrains lymphocyte differentiation, facilitated by H3K4me3 activating marks in genes that control the pre-B stage. Mutant cells undergo neoplastic transformation, and mice develop a highly penetrant B-cell leukaemia with multi-organ infiltration and early death. These renin-expressing cells appear uniquely vulnerable as other conditional models of RBP-J deletion do not result in leukaemia. The discovery of these unique renin progenitors in the bone marrow and the model of leukaemia described herein may enhance our understanding of normal and neoplastic haematopoiesis.

Can a minimal intervention reduce secondhand smoke exposure among children with asthma from low income minority families? Results of a randomized trial.

We report on the results of a low-intensity behavioral intervention to reduce second hand smoke (SHS) exposure of children with asthma from low income minority households in Los Angeles, California. In this study, 242 child/adult dyads were randomized to a behavioral intervention (video, workbook, minimal counseling) or control condition (brochure). Main outcome measures included child's urine cotinine and parental reports of child's hours of SHS exposure and number of household cigarettes smoked. Implementation of household bans was also considered. No differences in outcomes were detected between intervention and control groups at follow-up. Limitations included high attrition and low rates of collection of objective measures (few children with urine cotinine samples). There continues to be a need for effective culturally and linguistically appropriate strategies that support reduction of household SHS exposure among children with asthma in low income, minority households.

Mobile health care operations and return on investment in predominantly underserved children with asthma: the breathmobile program.

Underserved populations have limited access to care. Improved access to effective asthma care potentially improves quality of life and reduces costs associated with emergency department (ED) visits. The purpose of this study is to examine return on investment (ROI) for the Breathmobile Program in terms of improved patient quality-adjusted life years saved and reduced costs attributed to preventable ED visits for 2010, with extrapolation to previous years of operation. It also examines cost-benefit related to reduced morbidity (ED visits, hospitalizations, and school absenteeism) for new patients to the Breathmobile Program during 2008-2009 who engaged in care (≥3 visits). This is a retrospective analysis of data for 15,986 pediatric patients, covering 88,865 visits, participating in 4 Southern California Breathmobile Programs (November 16, 1995-December 31, 2010). The ROI calculation expressed the cost-benefit ratio as the net benefits (ED costs avoided+relative value of quality-adjusted life years saved) over the per annum program costs (∼$500,000 per mobile). The ROI across the 4 California programs in 2010 was $6.73 per dollar invested. Annual estimated emergency costs avoided in the 4 regions were $2,541,639. The relative value of quality-adjusted life years saved was $24,381,000. For patients new to the Breathmobile Program during 2008-2009 who engaged in care (≥3 visits), total annual morbidity costs avoided per patient were $1395. This study suggests that mobile health care is a cost-effective strategy to deliver medical care to underserved populations, consistent with the Triple Aims of Therapy.

Control of renin [corrected] gene expression.

Renin, as part of the renin-angiotensin system, plays a critical role in the regulation of blood pressure, electrolyte homeostasis, mammalian renal development, and progression of fibrotic/hypertrophic diseases. Renin gene transcription is subject to complex developmental and tissue-specific regulation. Initial studies using the mouse As4.1 cell line, which has many characteristics of the renin-expressing juxtaglomerular cells of the kidney, have identified a proximal promoter region (-197 to -50 bp) and an enhancer (-2,866 to -2,625 bp) upstream of the Ren-1(c) gene, which are critical for renin gene expression. The proximal promoter region contains several transcription factor binding sites including a binding site for the products of the developmental control genes Hox. The enhancer consists of at least 11 transcription factor binding sites and is responsive to various signal transduction pathways including cAMP, retinoic acid, endothelin-1, and cytokines, all of which are known to alter renin mRNA levels. Furthermore, in vivo models have validated several of these key components found within the proximal promoter region and the enhancer as well as other key sites necessary for renin gene transcription.

Protective effects against abortion and fetal infection following exposure to bovine viral diarrhea virus and bovine herpesvirus 1 during pregnancy in beef heifers that received two doses of a multivalent modified-live virus vaccine prior to breeding.

OBJECTIVE: To determine whether administration of 2 doses of a multivalent, modified-live virus vaccine prior to breeding of heifers would provide protection against abortion and fetal infection following exposure of pregnant heifers to cattle persistently infected (PI) with bovine viral diarrhea virus (BVDV) and cattle with acute bovine herpesvirus 1 (BHV1) infection. DESIGN: Randomized controlled clinical trial. ANIMALS: 33 crossbred beef heifers, 3 steers, 6 bulls, and 25 calves. PROCEDURES: 20 of 22 vaccinated and 10 of 11 unvaccinated heifers became pregnant and were commingled with 3 steers PI with BVDV type 1a, 1b, or 2 for 56 days beginning 102 days after the second vaccination (administered 30 days after the first vaccination). Eighty days following removal of BVDV-PI steers, heifers were commingled with 3 bulls with acute BHV1 infection for 14 days. RESULTS: After BVDV exposure, 1 fetus (not evaluated) was aborted by a vaccinated heifer; BVDV was detected in 0 of 19 calves from vaccinated heifers and in all 4 fetuses (aborted after BHV1 exposure) and 6 calves from unvaccinated heifers. Bovine herpesvirus 1 was not detected in any fetus or calf and associated fetal membranes in either treatment group. Vaccinated heifers had longer gestation periods and calves with greater birth weights, weaning weights, average daily gains, and market value at weaning, compared with those for calves born to unvaccinated heifers. CONCLUSIONS AND CLINICAL RELEVANCE: Prebreeding administration of a modified-live virus vaccine to heifers resulted in fewer abortions and BVDV-PI offspring and improved growth and increased market value of weaned calves.

Achieving and maintaining asthma control in inner-city children.

BACKGROUND: Despite guidelines-defined care, inner-city children of low socioeconomic status have poor asthma control. OBJECTIVE: This study evaluated time to achieve control, maintenance of control, and factors associated with well controlled asthma for pediatric patients receiving specialty-based asthma care in mobile asthma clinics designed to reduce barriers to delivering effective asthma care (the Breathmobile Program). METHODS: Existing clinical data collected from January 1998 to June 2008 for 7822 pediatric patients with asthma (34,339 visits) enrolled in similarly structured mobile asthma programs across the United States evaluated the effect of asthma control on the reduction of asthma-related morbidity, time to achieve asthma control, maintenance of asthma control, and factors associated with well controlled asthma. RESULTS: Comparison of pre and post year data for subjects enrolled in the program for at least 1 year revealed reductions in the percentage of patients reporting emergency department visits (mean, 66%), hospitalizations (mean, 84%), and missed school days ≥5/year (mean, 78%). Well controlled asthma was achieved by visit 3 for an estimated 80% of patients. Factors contributing to well controlled asthma include non-African American race, visit interval <90 days, and adherence to prescribed therapy. CONCLUSION: This study demonstrates the ability to achieve and maintain asthma control in high-risk populations in association with intensive, accessible, guidelines-defined care with close follow-up.

The Back to School asthma study: the effect of montelukast on asthma burden when initiated prophylactically at the start of the school year.

BACKGROUND: Pediatric asthma hospitalizations peak in early autumn. OBJECTIVE: To determine the effectiveness of montelukast therapy in reducing the asthma burden in children when initiated prophylactically on school return. METHODS: This was a randomized, multicenter, double-blind, placebo-controlled study of children with asthma aged 6 to 14 years. No minimum asthma symptoms were required, and patients could continue inhaled corticosteroid (ICS) use. Montelukast, 5 mg, chewable tablet (n = 580) or matching placebo (n = 582) was taken the night before the first day of school and nightly thereafter for 8 weeks. The primary end point was the percentage of days with worsening asthma, defined by one of the following: (1) increased beta-agonist use, (2) increased daytime symptoms, (3) awake "all night," (4) oral corticosteroid rescue or increased ICS use for worsening asthma, or (5) unanticipated health care utilization. RESULTS: The reduction in the percentage of days with worsening asthma with montelukast use versus placebo use was not significant (24.3% vs 27.2%, P = .07). Prespecified subgroup analyses demonstrated nonsignificant trends favoring montelukast therapy in boys and older children but no effect by baseline ICS use or history of cold symptoms. Post hoc analysis showed a nonsignificant trend favoring montelukast therapy in reducing worsening asthma days for children commencing school after August 15 compared with earlier commencement. CONCLUSIONS: Montelukast use was not significantly more effective than was placebo use in reducing the percentage of days with worsening asthma when initiated at the start of the school year. The effect of montelukast treatment on the fall peak in asthma burden may depend on sex, age, and the date of school return.

Asthma control and activity limitations: insights from the Real-world Evaluation of Asthma Control and Treatment (REACT) study.

BACKGROUND: Uncontrolled asthma remains prevalent in the United States and confers a substantial burden on the health care system. OBJECTIVES: To evaluate the association between uncontrolled asthma and activity limitations in a nationally representative sample of patients with moderate-to-severe-treated asthma and to assess the degree to which demographics and comorbidities were associated with activity limitations. METHODS: Patients who participated in the Real-world Evaluation of Asthma Control and Treatment study were surveyed regarding type and degree of activity limitations in 4 categories: outdoor activity, physical activity, daily activity, and environmental triggers. Information about asthma control, demographics, and comorbidities was collected. Multivariable regression was used to assess the association between uncontrolled asthma and activity limitations while adjusting for demographic characteristics and comorbid conditions. RESULTS: Uncontrolled asthma was associated with a greater than 2-fold risk of outdoor (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.90-3.51) or physical (OR, 2.62; 95% CI, 1.90-3.61) activity limitations and a 66% increased risk of daily activity limitations (OR, 1.66; 95% CI, 1.09-2.51). Comorbidities associated with activity limitation included hives, chronic sinusitis, arthritis, gastroesophageal reflux disease, hypercholesterolemia, and depression. The observed associations between uncontrolled asthma and activity limitation remained significant after controlling for demographic characteristics and comorbid conditions. CONCLUSIONS: Compared with patients with controlled asthma, those with uncontrolled asthma are at higher risk for limitations in outdoor activity, physical activity, and daily activity. To help patients achieve optimal health, asthma management should include routine assessment of activity limitations and assessment and coordinated care for comorbid conditions.

Predicting asthma control using patient attitudes toward medical care: the REACT score.

BACKGROUND: The association between patients' degree of asthma control and their attitudes toward medical professionals and asthma therapy is unknown. OBJECTIVE: To develop a tool, the REACT Score, that can be used by physicians to compute the risk of having uncontrolled asthma based on patient attitudes toward medical professionals and asthma treatment. METHODS: A nationally representative sample of adult patients (> or = 18 years old) with moderate to severe asthma completed the Asthma Control Test and were surveyed regarding their attitudes about relationships with medical professionals and asthma treatments. Competing predictive models were developed to determine the association between attitude questions and asthma control. Using the model with the highest c-index, a REACT Score was computed. RESULTS: The proportion of uncontrolled patients (Asthma Control Test score < 20) in the high-, medium-, and low-risk REACT Score categories was 75%, 50%, and 24%, respectively. Patients who believed that their physician recognized lifestyle compromises due to asthma, who were not satisfied with their treatment regimen, and who took asthma medication more frequently than prescribed had a higher risk of poor asthma control. CONCLUSION: The REACT Score is a novel way to predict asthma control and to identify key attitudes and behaviors that need to be addressed to engage a patient in ongoing, effective care. This tool may also improve communication between asthmatic patients and their physicians by identifying patient concerns regarding their treatment and quality of life.

In vivo analysis of key elements within the renin regulatory region.

Renin is responsible for initiating the enzymatic cascade that results in the production of angiotensin II, the major effector molecule of the renin-angiotensin system (RAS). Extensive information on the regulatory region of the renin gene has been derived by transient transfection studies in vitro, particularly using the As4.1 cell line. To verify key factors within the regulatory region of renin in vivo, homologous recombination was used to introduce a green fluorescent protein (GFP) cassette into exon one of the renin gene contained within a 240 kb bacterial artificial chromosome (BAC) to create a construct that has GFP expression controlled by the renin regulatory region (RenGFP BAC). Within the regulatory region of the RenGFP BAC construct we independently deleted the enhancer, as well as mutated the HOX-PBX site within the proximal promoter element. Transgenic lines were generated for each of these BAC constructs and GFP expression was analyzed throughout a spectrum of tissues positive for renin expression including the kidney, adrenal gland, gonadal artery, and submandibular gland. The results described within this manuscript support the interpretation that the renin enhancer is critical for regulating baseline expression where as the Hox/Pbx site is important for the tissue specificity of renin expression.

Asthma control and future asthma-related morbidity in inner-city asthmatic children.

BACKGROUND: Asthma guidelines recommend routine evaluation of asthma control, which includes measurements of impairment and risk. It is unclear whether rigorous asthma control changes risk of asthma morbidity. OBJECTIVE: To examine whether the degree of asthma control in inner-city asthmatic children results in differential risk reduction of future asthma-related morbidity. METHODS: This retrospective observational study examines 960 inner-city children with asthma who were highly engaged in an asthma-specific disease management program for a minimum of 2 years. Degree of asthma control was determined during the first year of enrollment and was categorized as well controlled (> or = 80% of visits in control), moderately controlled (50%-79% of visits in control), or difficult to control (< 50% of visits in control). Risk and probability of asthma-related morbidity at each visit were determined during the second year of enrollment and included self-reported asthma exacerbations requiring systemic corticosteroid rescue and emergency department visits or hospitalizations. RESULTS: Increasing the degree of asthma control measured during the first year of enrollment led to statistically significant incremental reductions in risk of acute asthma exacerbations and emergency department visits or hospitalizations during the second year of enrollment. CONCLUSIONS: Achieving and maintaining asthma control in inner-city children with asthma results in significant reductions in asthma-related morbidity. Systematic assessments of asthma control may be useful for predicting future risk in children with asthma.

Longitudinal patterns of predominant asthma disease activity in pediatric patients enrolled in an asthma-specific disease management program.

To determine if patterns of predominant asthma disease activity are more closely related than baseline asthma severity to measures of morbidity (acute asthma attack, emergency room visit/hospitalization, missed school days, and/or steroid burst). Retrospective analysis was performed for inner-city Los Angeles asthmatic children (3 to 18 years of age) during their first year of enrollment in an asthma-specific disease management program. All measures of morbidity were more closely related to patterns of predominant disease activity than baseline severity. We conclude that patterns of predominant disease activity are a more significant predictor of asthma morbidity than is baseline severity.

Health disparities in the United States: childhood asthma.

During the last 3 decades, asthma prevalence and morbidity in the United States have dramatically increased. The impact of this chronic respiratory disease has been disproportionately high among inner city residents, particularly lower socioeconomic groups, ethnic minorities, and children. A wide variety of factors have been shown to have an influence-indeed, the asthma epidemic is a chronicle of the ways in which environmental, social, and economic factors superimposed on inadequate health care delivery systems can converge to influence health status and the course of a chronic disease. Effective intervention strategies for this controllable disease must circumvent existing societal barriers to care and provide a comprehensive, structured program that emphasizes asthma controller therapy, disease-specific education, and regular periodic assessment of asthma control, preferably in a convenient, familiar setting that promotes patient engagement.

The chakragati mouse shows deficits in prepulse inhibition of acoustic startle and latent inhibition.

The chakragati (ckr) mouse, which was serendipitously created as a result of a transgenic insertional mutation, has been proposed as a model of aspects of schizophrenia. The mice exhibit circling, hyperactivity, reduced social interactions, and enlarged lateral ventricles, which parallel aspects of the pathophysiology of schizophrenia. Deficits in sensorimotor gating and processing of the relevance of stimuli are core features of schizophrenia, which underlie many of the symptoms presented. Measures of prepulse inhibition (PPI) and latent inhibition (LI) can assess sensorimotor gating and processing of relevance in both humans and animal models. We investigated PPI of acoustic startle and LI of aversive conditioning in wild-type, heterozygous, and ckr mice. The ckr mice, which are homozygous for the transgene insertion, but not heterozygous littermates, showed impaired PPI in the absence of any difference in acoustic startle amplitude and showed deficits in LI of conditioning of a light stimulus to footshock, measured as suppression of licking for water in water-restricted mice. Together with the previous evidence for hyperactivity, reduced social interactions, and enlarged lateral ventricles, these data lend further support to the suggestion that the ckr mouse has utility as an animal model of aspects of schizophrenia.

Expression profiling of archival renal tumors by quantitative PCR to validate prognostic markers.

Formalin-fixed paraffin-embedded (FFPE) tissues are routinely stored by most pathology departments and are a widely available resource for discovery of clinically useful biomarkers. We describe our method for optimizing quantitative reverse transcription PCR (RT-PCR) for expression analysis using frozen and archival tissue. Commonly used reference genes were evaluated for stability of expression in normal kidney and clear cell renal cell carcinoma (RCC). Optimal reference genes for calculating normalization factors for RT-PCR were ACTB, RPL13A, GUS, RPLP0, HPRT1, and SDHA when using FFPE RCC. The optimal reference genes when using frozen RCC were ACTB, RPL13A, and GUS, confirming that use of multiple reference genes improves accuracy when intact RNA from frozen renal tumors are used. Expression of 16 markers previously reported to have prognostic significance in RCC was determined in 23 matching frozen and FFPE renal tumors, representing a range of tumor grades and stages; correlation coefficient for expression measured in frozen and FFPE tumors was 0.921 (P < 0.001). All markers predicted survival when frozen tumors were used and 14 of the 16 markers predicted survival when FFPE tumors were used as the source of RNA. An optimized RT-PCR assay can accurately measure expression of most prognostic tumor markers.

Real-world Evaluation of Asthma Control and Treatment (REACT): findings from a national Web-based survey.

BACKGROUND: Despite health initiatives for advancing the management of asthma, evidence suggests that many asthmatic subjects have uncontrolled disease. However, the prevalence of uncontrolled asthma in the United States is not known and has not been fully characterized. OBJECTIVE: We sought to assess the prevalence, morbidity, and factors associated with uncontrolled asthma in a nationally representative sample of patients with moderate-to-severe asthma using standard asthma medications. METHODS: A Web-based survey was administered to patients with diagnoses of asthma for at least 1 year who were receiving multiple controller medications. The Asthma Control Test score was used to stratify respondents into controlled and uncontrolled cohorts. RESULTS: A total of 1812 patients were assessed; 809 (45%) had controlled asthma, and 1003 (55%) had uncontrolled asthma. Most patients had health care coverage and received care from a general practitioner; a large proportion of patients with controlled asthma (74%) and patients with uncontrolled asthma (65%) reported never receiving an asthma action plan. Inhaled corticosteroid plus long-acting beta-agonist was the most common medication regimen in patients with controlled asthma (60%) and patients with uncontrolled asthma (48%) patients. Patients with uncontrolled asthma reported significantly higher rates of health care use. Several comorbidities were predictive of uncontrolled asthma. CONCLUSION: Uncontrolled asthma is highly prevalent (55%) in patients using standard asthma medications. There is need for improved asthma care in patients with moderate-to-severe asthma, including a global evaluation of asthma control, implementation of treatment plans and asthma control tests, and addressing comorbid conditions. CLINICAL IMPLICATIONS: Improved asthma care requires broader assessments of asthma control, including asthma-related health care and medication use, comorbidities, and the implementation of treatment plans and formal asthma control tests.

Achieving and maintaining asthma control in an urban pediatric disease management program: the Breathmobile Program.

BACKGROUND: National guidelines suggest that, with appropriate care, most patients can control their asthma. The probabilities of children achieving and maintaining control with ongoing care are unknown. OBJECTIVE: We sought to evaluate the degree to which children in a lower socioeconomic urban setting achieve and maintain control of asthma with regular participation in a disease management program that provides guideline-based care. METHODS: Interdisciplinary teams of asthma specialists use mobile clinics to offer ongoing care at schools and county clinics. A guideline-derived construct of asthma control is recorded at each visit. RESULTS: Two thousand one hundred eighty-five enrollees were eligible to evaluate the time to first achieve control, and 1591 patients were eligible to evaluate subsequent control maintenance. Depending on severity, 70% to 87% of patients with persistent asthma achieved control by visit 3, and 89% to 98% achieved control by visit 6. Subsequent control maintenance was highly variable. Thirty-nine percent of patients displayed well-controlled asthma (control at >90% of subsequent visits), whereas 13% displayed difficult-to-control asthma (<50% of subsequent visits). Patients from each baseline severity category were found in each group. Maintenance of control was influenced by physician-estimated compliance with the treatment plan, baseline severity, and the interval between clinic visits. CONCLUSIONS: Many children can achieve asthma control with regular visit intervals and guideline-based care; however, long-term control can be highly variable among patients in all severity categories. CLINICAL IMPLICATIONS: These findings highlight the need and feasibility for systematically tracking each patient's clinical response to individualize therapy and guide the use of population management strategies.