Correcting for missing and irregular data in home-range estimation.

Home-range estimation is an important application of animal tracking data that is frequently complicated by autocorrelation, sampling irregularity, and small effective sample sizes. We introduce a novel, optimal weighting method that accounts for temporal sampling bias in autocorrelated tracking data. This method corrects for irregular and missing data, such that oversampled times are downweighted and undersampled times are upweighted to minimize error in the home-range estimate. We also introduce computationally efficient algorithms that make this method feasible with large data sets. Generally speaking, there are three situations where weight optimization improves the accuracy of home-range estimates: with marine data, where the sampling schedule is highly irregular, with duty cycled data, where the sampling schedule changes during the observation period, and when a small number of home-range crossings are observed, making the beginning and end times more independent and informative than the intermediate times. Using both simulated data and empirical examples including reef manta ray, Mongolian gazelle, and African buffalo, optimal weighting is shown to reduce the error and increase the spatial resolution of home-range estimates. With a conveniently packaged and computationally efficient software implementation, this method broadens the array of data sets with which accurate space-use assessments can be made.

Movement ecology of vulnerable lowland tapirs between areas of varying human disturbance.

BACKGROUND: Animal movement is a key ecological process that is tightly coupled to local environmental conditions. While agriculture, urbanisation, and transportation infrastructure are critical to human socio-economic improvement, these have spurred substantial changes in animal movement across the globe with potential impacts on fitness and survival. Notably, however, human disturbance can have differential effects across species, and responses to human activities are thus largely taxa and context specific. As human disturbance is only expected to worsen over the next decade it is critical to better understand how species respond to human disturbance in order to develop effective, case-specific conservation strategies. METHODS: Here, we use an extensive telemetry dataset collected over 22 years to fill a critical knowledge gap in the movement ecology of lowland tapirs (Tapirus terrestris) across areas of varying human disturbance within three biomes in southern Brazil: the Pantanal, Cerrado, and Atlantic Forest. RESULTS: From these data we found that the mean home range size across all monitored tapirs was 8.31 km2 (95% CI 6.53-10.42), with no evidence that home range sizes differed between sexes nor age groups. Interestingly, although the Atlantic Forest, Cerrado, and Pantanal vary substantially in habitat composition, levels of human disturbance, and tapir population densities, we found that lowland tapir movement behaviour and space use were consistent across all three biomes. Human disturbance also had no detectable effect on lowland tapir movement. Lowland tapirs living in the most altered habitats we monitored exhibited movement behaviour that was comparable to that of tapirs living in a near pristine environment. CONCLUSIONS: Contrary to our expectations, although we observed individual variability in lowland tapir space use and movement, human impacts on the landscape also had no measurable effect on their movement. Lowland tapir movement behaviour thus appears to exhibit very little phenotypic plasticity in response to human disturbance. Crucially, the lack of any detectable response to anthropogenic disturbance suggests that human modified habitats risk being ecological traps for tapirs and this information should be factored into conservation actions and species management aimed towards protecting lowland tapir populations.

Oviductal extracellular vesicles interact with the spermatozoon's head and mid-piece and improves its motility and fertilizing ability in the domestic cat.

Fertilization and early embryo development are regulated by a unique maternal-gamete/embryo cross-talk within the oviduct. Recent studies have shown that extracellular vesicles (EVs) within the oviduct play important roles in mediating this developmental process. Here, we examined the influence of oviductal EVs on sperm function in the domestic cat. We demonstrated that (1) EVs are enriched in proteins related to energy metabolism, membrane modification, and reproductive function; (2) EVs bound and fused with the membranes of the acrosome and mid piece; and (3) incubating sperm with EVs improved motility, fertilizing capacity of cat spermatozoa and prevented acrosomal exocytosis in vitro. These findings indicated that oviductal EVs mediate sperm function and fertilization in the cat and provides new insights to improve sperm cryopreservation and in vitro fertilization in the domestic and wild felids and human.

Rensching cats and dogs: feeding ecology and fecundity trends explain variation in the allometry of sexual size dimorphism.

The tendency for sexual size dimorphism (SSD) to increase with body mass in taxa where males are larger, and to decrease when females are larger, is known as Rensch's rule. In mammals, where the trend occurs, it is believed to be the result of a competitive advantage for larger males, while female mass is constrained by the energetics of reproduction. Here, we examine the allometry of SSD within the Felidae and Canidae, demonstrating distinctly different patterns: in felids, there is positive allometric scaling, while there is no trend in canids. We hypothesize that feeding ecology, via its effect on female spacing patterns, is responsible for the difference; larger male mass may be advantageous only where females are dispersed such that males can defend access to them. This is supported by the observation that felids are predominately solitary, and all are obligate carnivores. Similarly, carnivorous canids are more sexually dimorphic than insectivores and omnivores, but carnivory does not contribute to a Rensch effect as dietary variation occurs across the mass spectrum. The observed inter-familial differences are also consistent with reduced constraints on female mass in the canids, where litter size increases with body mass, versus no observable allometry in the felids.

A laboratory study of bacteria-facilitated cadmium transport in alluvial gravel aquifer media.

Colloids, including bacteria, can dramatically accelerate the transport of heavy metals in ground water. Batch and column experiments were conducted to investigate adsorption of cadmium (Cd) onto Bacillus subtilis spores or Escherichia coli vegetative cells and Cd transport in alluvial gravel aquifer media in the presence of these bacteria. Results of the batch experiments showed that adsorption of Cd onto the bacteria was (i) positively related to solution pH, bacterial concentration, and negative surface charge, but inversely related to Cd concentration and (ii) a rate-limited nonlinear process, but adsorption onto E. coli was much less. For column influent Cd concentrations of about 4 mg/L and bacterial concentrations of > or = 10(5) colony-forming units (cfu)/mL, there was a significant increase in total Cd effluent concentrations. In comparison with controls that did not have bacteria-facilitated transport, Cd traveled 17 to 20 times faster when it traveled with mobile bacteria. However, Cd traveled mostly 2 to 3 times slower during the desorption phase under the influence of bacteria retained in the column. The difference between total and dissolved Cd concentrations was significant during Cd cotransport with B. subtilis spores, but this concentration difference was very small during Cd cotransport with E. coli, suggesting an adsorption-dominant mechanism during Cd cotransport with the spores and the possibility of Cd chelation by the dissolved membrane vesicles secreted from E. coli cell walls. Bacteria-facilitated transport of heavy metals may pose a threat to ground water quality in sites such as landfills and following land disposal of industrial and domestic effluent and sludge.

The effect of Duddingtonia flagrans on trichostrongyle infections of Saanen goats on pasture.

Four groups of nine Saanen goat does with a naturally acquired mixed trichostrongylid infection were grazed on four paddocks. Two groups received a daily dose of Duddingtonia flagrans at the rate of 5 x 10(7) chlamydospores per animal per day for the 26-day grazing period. After a 19-day pasture resting period, 20 worm free 12-week-old tracer kids were introduced to the paddocks for 14 days prior to removal for worm burden analysis. Four groups of five does and four kids were drenched then turned out onto the paddocks and faecal egg count (FEC) monitored. The FEC between groups was comparable throughout the initial grazing period. There were significant reductions in number of Teladorsagia circumcincta (54.8%, P=0.004) and Haemonchus contortus (85.0%, P=0.02) worms recovered from tracer animals. FEC of animals subsequently grazing pasture were significantly reduced (P=0.036) with reductions of 44% observed 4 weeks post-turnout. No significant difference was observed after 6 weeks grazing. This trial has demonstrated the potential of D. flagrans to reduce larval numbers on pasture grazed by goats under New Zealand conditions.

Once-daily cetirizine effective in the treatment of seasonal allergic rhinitis in children aged 6 to 11 years: a randomized, double-blind, placebo-controlled study.

Cetirizine (once daily), a highly selective H1-antagonist, is efficacious for treating seasonal allergic rhinitis (SAR), perennial allergic rhinitis, and chronic idiopathic urticaria. A 4-week, randomized, double-blind, placebo-controlled trial investigated the safety and efficacy of cetirizine syrup (5 or 10 mg daily) in 209 children ages 6 to 11 years with SAR. Parents assisted patients in recording symptom severity (sneezing, nasal discharge, itchy eyes, itchy nose or mouth, conjunctivitis, nasal congestion) daily. A total symptom severity (TSS) score was derived from all symptoms, excluding nasal congestion. At baseline, TSS was comparable for all groups (range 6.8-7.0). Cetirizine 10 mg produced a significantly greater mean TSS reduction (3.2) than placebo (P < 0.05) over the treatment period. Cetirizine 5 mg once daily produced mean reductions in weekly symptom scores of 2.4; this did not differ statistically from placebo. Furthermore, cetirizine 10 mg significantly improved symptoms of itchy eyes, nose, or mouth. The most commonly reported adverse reactions to both cetirizine and placebo were headache, pharyngitis, and abdominal pain, which did not occur with an incidence statistically different from that of placebo. Once-daily cetirizine is safe for treating SAR in children ages 6-11 years. Once-daily cetirizine 10 mg provides effective improvement in symptoms and is well tolerated.

Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients.

OBJECTIVE: To determine the ability of montelukast, a leukotriene receptor antagonist, to allow tapering of inhaled corticosteroids in clinically stable asthmatic patients. DESIGN: Double blind, randomised, placebo controlled, parallel group study. After a single blind placebo run in period, during which (at most) two inhaled corticosteroids dose decreases occurred, qualifying, clinically stable patients were allocated randomly to receive montelukast (10 mg tablet) or matching placebo once daily at bedtime for up to 12 weeks. SETTING: 23 academic asthma centres in United States, Canada, and Europe. PARTICIPANTS: 226 clinically stable patients with chronic asthma receiving high doses of inhaled corticosteroids (113 randomised to montelukast and 113 to placebo). INTERVENTIONS: Every 2 weeks, the inhaled corticosteroids dose was tapered, maintained, or increased (rescue) based on a standardised clinical score. MAIN OUTCOME MEASURES: Last tolerated dose of inhaled corticosteroids. RESULTS: Compared with placebo, montelukast allowed significant (P=0. 046) reduction in the inhaled corticosteroid dose (montelukast 47% v placebo 30%; least square mean difference 17.6%, 95% confidence interval 0.3 to 34.8). Fewer patients on montelukast (18 (16%) v 34 (30%) placebo, P=0.01) required discontinuation because of failed rescue. CONCLUSIONS: Montelukast reduces the need for inhaled corticosteroids among patients requiring moderate to high doses of corticosteroid to maintain asthma control.

Aspergillus antibody in patients with cystic fibrosis.

The respiratory flora of patients with cystic fibrosis (CF) frequently includes Aspergillus, and 30% of their serum samples have been observed to contain precipitating antibody to this fungus. Serum from 61 CF patients, 60 healthy persons, and three patients with CF and allergic bronchopulmonary aspergillosis was studied, using a quantitative assay for antibody to A fumigatus. Although CF patients had significantly higher levels of Aspergillus antibody, some antibody was found in all serum samples from normal individuals. Binding was immunologically specific for A fumigatus. Serum IgE levels and dermal reactivity to Aspergillus were similar in both CF and normal subjects. Increased levels of Aspergillus antibody in CF patients probably reflect pulmonary colonization, which only rarely causes infection or sensitization.

Dose-related response to inhaled fluticasone propionate in patients with methacholine-induced bronchial hyperresponsiveness: a double-blind, placebo-controlled study.

Dose-response relationships with inhaled corticosteroids in the treatment of asthma have been difficult to establish. A multicenter, double-blind, parallel-group study was conducted to evaluate the clinical efficacy and safety of low doses of inhaled fluticasone propionate (FP) in patients with mild to moderate asthma. Methacholine challenge testing was conducted in addition to measurement of traditional efficacy variables. After a single-blind screening period, 138 patients > or = 12 years of age were randomly assigned to receive placebo, FP 50 microg, or FP 100 microg, twice daily for 8 weeks. The results of methacholine challenge testing averaged over all visits favored FP 200 microg/day over placebo and FP 100 microg/day (p < 0.05); there were no significant differences between placebo and FP 100 microg/day. Mean changes from baseline to endpoint favored each dose of FP over placebo based on forced expiratory volume in 1 sec (FEV1), patient-measured peak expiratory flow (PEF), total symptom scores, and rescue bronchodilator use (p < 0.05); there were no differences in these parameters between the two doses of FP. The addition of methacholine challenge testing allowed definition of a dose-response relationship that was not apparent with traditional efficacy variables.

Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in chronic asthma. Montelukast Asthma Study Group.

The leukotrienes are known to be important mediators of bronchial asthma. The ability of montelukast, a potent and selective CysLT1 leukotriene receptor antagonist, to cause a dose-related improvement in chronic asthma was investigated in a placebo-controlled, multicentre, parallel-group study. After a two week placebo run-in period, chronic asthmatic patients with a forced expiratory volume in one second (FEV1) 40-80% predicted with > or = 15% increase (absolute value) after beta2-agonist were randomly assigned to one of four treatment groups (placebo or montelukast 2, 10, or 50 mg once daily in the evening) for a three week, double-blind treatment period. For patient-reported end-points (daytime symptom score, use of as needed inhaled beta2 agonist, asthma-specific quality of life) and frequency of asthma exacerbations, montelukast 10 and 50 mg caused similar responses, superior to 2 mg and significantly (p<0.05; linear trend test) different from placebo. All three doses caused improvements in FEV1 and morning and evening peak expiratory flow rate (PEFR) that were significantly (p<0.05) different from placebo. Differences (least square mean) between the pooled 10 and 50 mg montelukast treatment groups and placebo were: 7.1% change from baseline in FEV1, 19.23 L x min(-1) in morning PEFR, -0.29 in daytime asthma symptom score (absolute value), and -0.82 in beta2-agonist use (puff x day(-1)). The incidence of adverse experiences was neither dose-related nor different between montelukast and placebo treatments. We conclude that montelukast causes a dose-related improvement in patient-reported asthma end-points over the range 2-50 mg. Montelukast causes benefit to chronic asthmatic patients by improving asthma control end-points.

The health-related quality of life effects of once-daily cetirizine HCl in patients with seasonal allergic rhinitis: a randomized double-blind, placebo-controlled trial.

BACKGROUND: Seasonal allergic rhinitis (SAR) is characterized by subjectively irritating symptoms that can have a substantial impact on the patient's health-related quality of life (HRQL), adversely affecting physical and social or work activity, interpersonal relationships, and general psychological well-being. The objective of this study was to test the effect of cetirizine HCl 10 mg once daily on the HRQL of adult patients 18-65 years of age with SAR, concurrently assessing safety and efficacy. METHODS: Randomized double-blind, placebo-controlled, parallel group trial conducted during the 1999 spring SAR season at 19 centers in the US. Following a 1-week placebo run-in period, qualified patients were randomized to cetirizine 10 mg, or placebo once daily for a 2-week treatment period. Change in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Total Symptom Severity Complex (TSSC) scores from baseline were the primary outcomes of interest. RESULTS: Of the 611 patients enrolled, 403 (66%) were randomized. Cetirizine-treated patients reported significantly greater improvement in overall HRQL (P < 0.001) and in each of the seven domains of the RQLQ at all time-points (P < 0.05 to < 0.001) than the placebo group. They also experienced significantly greater symptom relief (P < 0.001) and were more satisfied with treatment (65% vs. 44%) compared to the placebo group. Correlations between symptomatic relief and overall HRQL improvement were moderate to strong and statistically significant (r = 0.49-0.68, P < 0.01). CONCLUSIONS: Results of this study are consistent with previous investigations, suggesting cetirizine HCl 10 mg taken once daily in the morning offers symptomatic relief that improves the HRQL of adults suffering from SAR.

Comparative efficacy and safety of twice daily fluticasone propionate powder versus placebo in the treatment of moderate asthma.

BACKGROUND: Fluticasone propionate, an inhaled corticosteroid with negligible systemic bioavailability via the oral route, is efficacious in the treatment of asthma when administered via metered-dose inhaler. OBJECTIVE: To evaluate the efficacy and safety of inhaled fluticasone propionate powder in patients with moderate asthma previously treated with an inhaled corticosteroid. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of 342 adolescent and adult patients with moderate asthma [forced expiratory volume in 1 second (FEV1) between 50% and 80% of predicted] treated previously by beclomethasone dipropionate or triamcinolone acetonide. Patients received fluticasone propionate powder 50 micrograms, 100 micrograms, 250 micrograms, or placebo via a breath-actuated inhalation device, the Diskhaler, twice daily for 12 weeks. RESULTS: Patients in the fluticasone propionate groups experienced a mean increase from baseline to endpoint in FEV1 ranging from 0.43 L to 0.47 L. Patients in the placebo group experienced a mean decrease from baseline of 0.22 L (P < .001). The probability of patients remaining in the study over time without developing signs of exacerbating asthma was significantly greater in the fluticasone propionate groups than in the placebo group (P = .001). Asthma symptom scores, supplemental rescue albuterol use, and number of nighttime awakenings due to asthma requiring treatment also improved significantly with all fluticasone propionate treatment regimens compared with placebo (P < .001). There were no statistically significant differences at endpoint among the three fluticasone propionate groups. No serious drug-related adverse events occurred. CONCLUSIONS: Fluticasone propionate powder (50, 100, and 250 micrograms) was well-tolerated and significantly improved lung function in patients with moderate asthma.

Effects of fluticasone propionate, triamcinolone acetonide, prednisone, and placebo on the hypothalamic-pituitary-adrenal axis.

BACKGROUND: Many clinicians are reluctant to prescribe inhaled corticosteroids because of concerns over potential effects on the hypothalamic-pituitary-adrenal axis. OBJECTIVE: The purpose of this study was to compare the adrenal responses to 6-hour cosyntropin infusion after treatment with fluticasone propionate aerosol, triamcinolone acetonide aerosol, prednisone, and placebo for 4 weeks, a sufficient time interval to assess any effects on the adrenal response to stress. METHODS: This double-blind, triple-dummy, randomized, placebo-controlled study was conducted in 128 patients to evaluate adrenal response to 6-hour cosyntropin infusion (a clinically relevant method for evaluating adrenal function) after 28 days of treatment with fluticasone propionate aerosol 88 microg or 220 microg twice daily, triamcinolone acetonide aerosol 200 microg 4 times daily or 400 microg twice daily, prednisone 10 mg once daily, and placebo. RESULTS: After 28 days of treatment, mean plasma cortisol response to cosyntropin over 12 hours after initiation of the 6-hour infusion was similar among fluticasone, triamcinolone, and placebo groups; cortisol response was significantly (P <.05) reduced after treatment with prednisone compared with the other treatment groups. Mean 8-hour area under the plasma cortisol concentration-time curves and peak plasma cortisol concentrations were significantly (P

Inhaled fluticasone propionate delivered by means of two different multidose powder inhalers is effective and safe in a large pediatric population with persistent asthma.

BACKGROUND: Inhaled corticosteroids are increasingly being used to treat mild-to-moderate asthma in children. However, data regarding therapy with this class of compounds, especially in children under age 6 years, is limited. Fluticasone propionate is a third generation inhaled corticosteroid with an optimal therapeutic index. Few large prospective clinical trials have been conducted to evaluate the efficacy and safety of fluticasone propionate powder in children. OBJECTIVE: We sought to determine the efficacy and safety of fluticasone propionate powder administered by means of the Diskus and Diskhaler multidose powder inhalers in pediatric patients with persistent asthma. METHODS: Fluticasone propionate powder (50 microg or 100 microg twice daily) or placebo was administered by means of the Diskus or Diskhaler inhalers to 437 children (4 to 11 years old) with persistent asthma for 12 weeks in a randomized, double-blind, parallel-group, multi-center trial. Patients were stratified according to whether they were receiving prior treatment with inhaled corticosteroids or cromolyn or beta2-agonists alone. RESULTS: Fluticasone propionate powder administered by means of Diskus or Diskhaler significantly improved FEV1 (mean increase from baseline of 0.22 to 0.24 L; p < or = 0.023), clinic morning peak expiratory flow (mean increase from baseline of 48 to 55 L/min; p < or = 0.006), patient-measured morning (p < or = 0.001) and evening (p < or = 0.003) peak expiratory flow, and asthma symptom scores (in all but the 50 microg Diskus group; p < or = 0.036), as well as reduced albuterol use (p < or = 0.002) and nighttime awakenings (p < or = 0.019) at endpoint. Efficacy parameters were not significantly different between the two doses with either device. More placebo-treated patients discontinued the study because of lack of efficacy than patients in any fluticasone propionate group (p < 0.001). Fluticasone propionate did not suppress morning plasma cortisol concentrations and did not affect 24-hour urinary free-cortisol excretion. Adverse events were primarily pharmacologic effects of inhaled corticosteroids, and those related to the study drug occurred with low frequency. Patient satisfaction with both the Diskus and Diskhaler devices was high, with a majority of patients (> 80%) rating them favorably. CONCLUSION: This study demonstrated that fluticasone propionate powder, at the conventional recommended doses of up to 200 microg/day administered by means of Diskus or Diskhaler, was well tolerated and improved lung function in children even as young as 4 and 5 years old regardless of whether they were previously treated with inhaled corticosteroids or cromolyn or beta2-agonists alone.

Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma.

BACKGROUND: Many patients with severe asthma are dependent on oral corticosteroids for maintenance control of their disease. Treatments that allow patients to be weaned off oral corticosteroids may help to minimize the risk of side effects associated with their chronic use. OBJECTIVE: This study evaluated whether inhaled fluticasone propionate powder could maintain pulmonary function while reducing the dose of oral prednisone in patients with chronic, severe asthma. METHODS: Oral prednisone-dependent (5 to 40 mg/day) adolescents and adults with asthma (n = 111; mean FEV1 = 61% of predicted value) were randomized to placebo or twice daily fluticasone propionate 500 or 1000 microg administered by means of a multidose powder inhaler for 16 weeks in a double-blind, parallel-group study. Patients underwent controlled prednisone reduction on the basis of predetermined asthma stability criteria. RESULTS: Oral prednisone was eliminated by 75% and 89% of patients in the twice daily 500 and 1000 microg fluticasone propionate groups, respectively, versus 9% of the placebo group (P <.001). FEV1, morning and evening peak expiratory flow, asthma symptoms, albuterol use, and nighttime awakenings improved with fluticasone propionate treatment, achieving statistical significance (P