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Purpose: Pseudoxanthoma elasticum (PXE) is a recessive disorder involving skin, eyes and arteries, mainly caused by ABCC6 pathogenic variants. However, almost one fifth of patients remain genetically unsolved despite extensive genetic screening of ABCC6, as illustrated in a large French PXE series of 220 cases. We searched for new PXE gene(s) to solve the ABCC6-negative patients.Methods: First, family-based exome sequencing was performed, in one ABCC6-negative PXE patient with additional neurological features, and her relatives. CYP2U1, involved in hereditary spastic paraplegia type 56 (SPG56), was selected based on this complex phenotype, and the presence of two candidate variants. Second, CYP2U1 sequencing was performed in a retrospective series of 46 additional ABCC6-negative PXE probands. Third, six additional SPG56 patients were evaluated for PXE skin and eye phenotype. Additionally, plasma pyrophosphate dosage and functional analyses were performed in some of these patients.Results: 6.4% of ABCC6-negative PXE patients (n = 3) harboured biallelic pathogenic variants in CYP2U1. PXE skin lesions with histological confirmation, eye lesions including maculopathy or angioid streaks, and various neurological symptoms were present. CYP2U1 missense variants were confirmed to impair protein function. Plasma pyrophosphate levels were normal. Two SPG56 patients (33%) presented some phenotypic overlap with PXE.Conclusion: CYP2U1 pathogenic variants are found in unsolved PXE patients with neurological findings, including spastic paraplegia, expanding the SPG56 phenotype and highlighting its overlap with PXE. The pathophysiology of ABCC6 and CYP2U1 should be explored to explain their respective role and potential interaction in ectopic mineralization. [ABSTRACT FROM AUTHOR]

Information about plant materials of construction in artefacts advances knowledge about human history, agriculture, trade, migration and adaptation to new environments. Typically, materials identification in artefacts made from plants is problematic, since processing, age, dirt and surface treatments can mask identifying features, while ethical considerations relating to sampling limit the use of some analytical techniques. The study tests the usefulness of polarized light microscopy for identifying the New Zealand and Pacific plant species used to make tapa, indicating birefringent and morphological characteristics that can be used to differentiate fibres at the level Moraceae (Pacific; from genera Artocarpus, Broussonetia and Ficus) and Malvaceae (New Zealand; from genera Hoheria and Plangianthus). [ABSTRACT FROM AUTHOR]

With the aim of mobilizing engineers and scientists to address environmental, climate, and energy justice challenges in the United States, this study examines how engineers and scientists view their incentives, barriers, and potential for community‐based collaborations. Through a purposive convenience sample (n = 281) and an online questionnaire, we investigate the attitudes and experiences of engineers and scientists regarding their community‐based work. Our analyses reveal dynamics of race, class, and experience, suggesting a type of socio‐demographic conditioning informing community‐based collaborations. Engineers and scientists also identify four main barriers to community‐based work: lack of time, lack of funding, lack of rapport, and knowledge deficits. In response, we introduce a field of collaboration with its own set of capitals—economic, cultural, social, and symbolic—and offer recommendations on how engineers, scientists, and community groups might collaborate with each other to address longstanding issues of energy, climate, and environmental injustice in the United States. Key Points: From a sample of n = 281, we examine how engineers/scientists view incentives, barriers, and potential for community‐based collaborationsWe find relations of race, class, and experience that suggests that sociodemographic conditioning informs community‐based collaborationsFour barriers to community collaborations are identified: lack of time, lack of funding, lack of rapport, and knowledge deficits [ABSTRACT FROM AUTHOR]

Summary: Objective: Excess body weight negatively impacts health, but there are few evaluations of low‐intensity weight management challenge programs in defined populations. This study examined weight change in adults who participated in the LOSE IT to WIN IT (LIWI) health challenge in a US community. The community‐level impact on body mass index was also explored. Methods: Body weight was analysed over 1 year in the cohort of LIWI enrolees, stratified by participants who were healthy weight or overweight/obese at baseline. Secondarily, a multiple cross‐sectional analysis compared the 2.5‐year trends in body mass index between community adults who did vs. did not participate in LIWI. Results: LOSE IT to WIN IT participants who were overweight/obese lost a mean (95% confidence interval) 1.6 (1.2, 2.0) kg (~2%) over 1 year (p < 0.001), whereas healthy weight participants lost 0.7 (0.3, 1.1) kg. Across the community, LIWI participants and non‐participants both gained 0.4 kg m−2 over the 2.5‐year study period (p = 0.884). Conclusions: LOSE IT to WIN IT was modestly effective among enrolees, resulting in a small weight loss of 2% over 1 year among those who were overweight/obese. However, LIWI did not impact weight gain in the community. To slow such community‐level weight gain trends, weight management challenges must reach larger fractions of the populations that they target. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of oclacitinib maleate was evaluated in four separate studies. The absolute bioavailability study used a crossover design with 10 dogs. The effect of food on bioavailability was investigated in a crossover study with 18 dogs. The breed effect on pharmacokinetics was assessed in a crossover study in beagles and mongrels dogs. Dose proportionality and multiple dose pharmacokinetics were evaluated in a parallel design study with eight dogs per group. In all four studies, serial blood samples for plasma were collected. Oclacitinib maleate was rapidly and well absorbed following oral administration, with a time to peak plasma concentration of <1 h and an absolute bioavailability of 89%. The prandial state of dogs did not significantly affect the rate or extent of absorption of oclacitinib maleate when dosed orally, as demonstrated by the lack of significant differences in pharmacokinetic parameters between the oral fasted and oral fed treatment groups. The pharmacokinetics of oclacitinib in laboratory populations of beagles and mixed breed dogs also appeared similar. Following oral administration, the exposure of oclacitinib maleate increased dose proportionally from 0.6 to 3.0 mg/kg. Additionally, across the pharmacokinetic studies, there were no apparent differences in oclacitinib pharmacokinetics attributable to sex. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of maropitant were evaluated in beagle dogs dosed orally with Cerenia® tablets ( Pfizer Animal Health) once daily for 14 consecutive days at either 2 mg/kg or 8 mg/kg bodyweight. Noncompartmental pharmacokinetic analysis was performed on the plasma concentration data to measure the AUC0-24 (after first and last doses), Ct (trough concentration-measured 24 h after each dose), Cmax (after first and last doses), tmax (after first and last doses), λz (terminal disposition rate constant; after last dose), t1/2 (after last dose), and CL/F (oral clearance; after last dose). Maropitant accumulation in plasma was substantially greater after fourteen daily 8 mg/kg doses than after fourteen daily 2 mg/kg doses as reflected in the AUC0-24 accumulation ratio of 4.81 at 8 mg/kg and 2.46 at 2 mg/kg. This is most likely due to previously identified nonlinear pharmacokinetics of maropitant in which high doses (8 mg/kg) saturate the metabolic clearance mechanisms and delay drug elimination. To determine the time to reach steady-state maropitant plasma levels, a nonlinear model was fit to the least squares ( LS) means maropitant Ct values for each treatment group. Based on this model, 90% of steady-state was determined to occur at approximately four doses for daily 2 mg/kg oral dosing and eight doses for daily 8 mg/kg oral dosing. [ABSTRACT FROM AUTHOR]

Collard, W. T., Cox, S. R., Lesman, S. P., Grover, G. S., Boucher, J. F., Hallberg, J. W., Robinson, J. A., Brown, S. A. Pharmacokinetics of ceftiofur crystalline-free acid sterile suspension in the equine. J. vet. Pharmacol. Therap. 34, 476-481. Absolute bioavailability and dose proportionality studies were performed with ceftiofur in horses. In the absolute bioavailability study, thirty animals received either an intravenous dose of ceftiofur sodium at 1.0 mg/kg or an intramuscular (i.m.) dose of ceftiofur crystalline-free acid (CCFA) at 6.6 mg/kg. In the dose proportionality study, 48 animals received daily i.m. ceftiofur sodium injections at 1.0 mg/kg for ten doses or two doses of CCFA separated by 96 h, with CCFA doses of 3.3, 6.6, or 13.2 mg/kg. Noncompartmental and mixed-effect modeling procedures were used to assess pharmacokinetics (PK). CCFA was well absorbed with a bioavailability of 100%. AUC0-∞ and Cmax increased in a dose-related manner following administration of the two doses of CCFA at 3.3, 6.6, and 13.2 mg/kg. The least-squares mean terminal half-life ( t½) following the tenth daily i.m. injection of ceftiofur sodium at 2.2 mg/kg was 40.8 h, but the least-squares mean t½ following the second i.m. injection of CCFA at 6.6 mg/kg was 100 h. The time that plasma ceftiofur equivalent concentrations remain above a threshold concentration of 0.2 μg/mL has been associated with efficacy, and following administration of two 6.6 mg/kg doses of CCFA, the mean time above 0.2 μg/mL was 262 h. Simulations with the nonlinear mixed-effect PK model predicted that more than 97.5% of horses will have plasma ceftiofur equivalent concentrations >0.2 μg/mL for 96 h after the second 6.6 mg/kg dose of CCFA. [ABSTRACT FROM AUTHOR]

Cox, S.R., Lesman, S.P., Boucher, J.F., Krautmann, M.J., Hummel, B.D., Savides, M., Marsh, S., Fielder, A., Stegemann, M.R. The pharmacokinetics of mavacoxib, a long-acting COX-2 inhibitor, in young adult laboratory dogs. J. vet. Pharmacol. Therap. 33, 461-470. The pharmacokinetics of mavacoxib were evaluated in an absolute bioavailability study, a dose-proportionality study and a multi-dose study in young healthy adult laboratory Beagle dogs and in a multi-dose safety study in Beagle-sized laboratory Mongrel dogs. When administered as the commercial tablet formulation at 4 mg/kg body weight (bw) to fasted dogs, the absolute bioavailability (F) of mavacoxib was 46.1%; F increased to 87.4% when mavacoxib was administered with food. Following intravenous administration, the total body plasma clearance of mavacoxib was 2.7 mL·h/kg, and the apparent volume of distribution at steady-state was 1.6 L/kg. The plasma protein binding of mavacoxib was approximately 98% in various in vitro and ex vivo studies. The dose-normalized area under the plasma concentration-time curve was similar in Beagle and Beagle-sized Mongrel dogs when mavacoxib was administered with food. Mavacoxib exhibited dose-proportional pharmacokinetics for single oral doses of 2-12 mg/kg in Beagle dogs and for multiple oral doses of 5-25 mg/kg in Beagle-sized Mongrel dogs. Only minor accumulation occurred when mavacoxib was administered at doses of 2-25 mg/kg bw orally to laboratory dogs with a 2-week interval between the 1st two doses but with a monthly interval thereafter. Across all three Beagle studies ( n = 63) the median terminal elimination half-life ( t½) was 16.6 days, with individual values ranging 7.9-38.8 days. The prolonged t½ for mavacoxib supports the approved regimen in which doses are separated by 2-4 weeks. [ABSTRACT FROM AUTHOR]

Yancey, M. F., Merritt, D. A., Lesman, S. P., Boucher, J. F., Michels, G. M. Pharmacokinetic properties of toceranib phosphate (Palladia™, SU11654), a novel tyrosine kinase inhibitor, in laboratory dogs and dogs with mast cell tumors. J. vet. Pharmacol. Therap. 33, 162–171. Toceranib phosphate (Palladia™, SU11654), an oral tyrosine-kinase inhibitor, is under investigation for the treatment of mast cell tumors in dogs. The pharmacokinetics of toceranib phosphate has been characterized in dogs. Means of the following pharmacokinetic parameters were estimated following a 1.0 mg/kg i.v. dose to laboratory beagles: plasma clearance of 1.45 L/kg/h, volume of distribution of 29.7 L/kg, and terminal half-life of 17.7 h. Following single oral doses of 3.25 mg/kg administered to laboratory beagles, mean Cmax estimates ranged from 68.6 ng/mL to 112 ng/mL with tmax ranging from 5.3 h and 9.3 h postdose. Terminal half-life was estimated at 31 h. Oral bioavailability was 76.9%. There were no statistically significant ( P > 0.05) differences with any pharmacokinetic parameter due to fed/fasted state or with time during 13 weeks of every-other-day dosing at 3.25 mg/kg. Toceranib concentrations were proportional with dose over the range of 2.0 to 6.0 mg/kg. The pharmacokinetics of toceranib in client-owned dogs of a variety of pure and mixed breeds with mast cell tumors was similar to that in healthy laboratory dogs. In summary, toceranib phosphate exhibited moderate clearance, a high volume of distribution, and a moderate elimination half-life. After a single oral dose at 3.25 mg/kg, the concentration vs. time curve showed broad, sustained exposure with measurable concentrations for more than 48 h. These pharmacokinetic parameters support every-other-day administration of toceranib phosphate at an initial dose of 3.25 mg/kg for the treatment of mast cell tumors in dogs. [ABSTRACT FROM AUTHOR]

Maropitant (Cerenia™), a selective neurokinin1 receptor antagonist, was evaluated for safety and efficacy in treatment and prevention of acute vomiting due to various etiologies in dogs in a randomized clinical trial. Two-hundred seventy-eight dogs were enrolled from 29 veterinary hospitals. Two-hundred fifty-two were evaluable for efficacy, while 275 were evaluable for safety. A randomized block design was utilized (three maropitant- and one placebo-treated dog per block). Initial treatment was maropitant at 1 mg/kg body weight (0.45 mg/lb) or an equivalent volume of saline (placebo) administered subcutaneously. On the subsequent 1 to 4 days, maropitant or placebo (dependent on allocation) was administered subcutaneously or orally at approximate 24-h intervals as needed. Oral doses were administered as maropitant tablets using unit dosing to deliver a minimum dose of 2 mg/kg body weight (0.9 mg/lb) or equivalent numbers of similar placebo tablets. Dogs and housing were observed twice daily for evidence of vomiting. Emesis was significantly ( P ≤ 0.0012) reduced in maropitant-treated dogs as 50% (32/64) of placebo-treated dogs continued to vomit compared to only 21.8% (41/188) of maropitant-treated dogs. Post-treatment clinical signs were consistent with clinical diagnoses and judged not to be treatment related. In this clinical trial, maropitant was safe and effective in reducing emesis due to various etiologies in dogs. [ABSTRACT FROM AUTHOR]

Maropitant (CereniaTM), a selective neurokinin1 receptor antagonist, was evaluated for efficacy and safety in prevention of vomiting due to motion sickness in dogs in two randomized clinical trials. One-hundred eighty-nine dogs with a history of motion sickness were enrolled at 26 veterinary clinics (across 12 US states) across the two trials; of these, 163 were fully evaluable, 19 were evaluable only for safety, and seven were not evaluable. Each trial used a two-period crossover design. Each dog was treated orally with placebo or maropitant (minimum dose of 8 mg/kg body weight using unit dosing) tablets at approximately 2 h (Trial 1) or 10 h (Trial 2) before an automobile ride of approximately 60 min, during which dogs were observed for signs of motion sickness. Following a 10–14-day washout period, each dog was administered the opposite treatment and taken for another journey (same route, driver and vehicle). Maropitant reduced the occurrence of vomiting compared to placebo by 86.1% or 76.5% when given approximately 2 or 10 h prior to travel, respectively. No significant clinical signs were observed after maropitant treatment. Maropitant was safe and effective in preventing vomiting due to motion sickness in dogs when administered at a minimum dose of 8 mg/kg body weight as oral tablets 2 or 10 h prior to travel. [ABSTRACT FROM AUTHOR]

Maropitant (Cerenia™; a novel, selective neurokinin1 receptor antagonist), chlorpromazine, metoclopramide and ondansetron were compared in two randomized, placebo-controlled studies for efficacy in preventing emesis induced by emetogens acting centrally (apomorphine; Study 1) or peripherally (syrup of ipecac; Study 2) in dogs. In each study, ten male and ten female beagles were treated in a five-treatment, five-period crossover design. The five treatments were 0.9% saline (0.1 mL/kg), maropitant (1 mg/kg), metoclopramide (0.5 mg/kg), or chlorpromazine (0.5 mg/kg) all administered subcutaneously, or ondansetron (0.5 mg/kg) administered intravenously. One hour posttreatment dogs were challenged with apomorphine at 0.1 mg/kg intravenously (Study 1) or syrup of ipecac at 0.5 mL/kg orally (Study 2). Following emetogen challenge, dogs were observed for 30 min (Study 1) or 1 h (Study 2) for emesis. No clinical signs, other than those related to emesis, were observed. Efficacy of maropitant in preventing emesis induced centrally by apomorphine was not different ( P > 0.05) from metoclopramide or chlorpromazine but was superior ( P < 0.0001) to ondansetron. Efficacy of maropitant in preventing emesis induced by syrup of ipecac was not different ( P > 0.05) from ondansetron but was superior ( P ≤ 0.0102) to metoclopramide or chlorpromazine. Maropitant was effective ( P < 0.0001 relative to control) in preventing vomiting caused by stimulation of either central or peripheral emetic pathways, whereas the other drugs examined prevented vomiting caused by central (metoclopramide and chlorpromazine; P < 0.0001) or peripheral (ondansetron; P < 0.0001) stimulation but not both. [ABSTRACT FROM AUTHOR]

The pharmacokinetic properties of cefpodoxime, and its prodrug, cefpodoxime proxetil, were evaluated in two separate studies, one following intravenous (i.v.) administration of cefpodoxime sodium and the second after oral (p.o.) administration of cefpodoxime proxetil to healthy dogs. After cefpodoxime administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). A single i.v. administration of cefpodoxime sodium at a dose of 10 mg  cefpodoxime/kg body weight resulted in a cefpodoxime average maximum plasma concentration ( Cmax) of 91 (±17.7) μg/mL, measured at 0.5 h after drug administration, an average half-life ( t1/2) of 4.67 (±0.680) h, an average AUC0−∞ of 454 (±83.1) h· μg/mL, an average Vd(ss) of 151 (±27) mL/kg, an average ClB of 22.7 (±4.2) mL/h/kg and an average MRT0−∞ of 5.97 (±0.573) h. When dose normalized to 10 mg  cefpodoxime/kg body weight, cefpodoxime proxetil administered orally resulted in Cmax of 17.8 ± 11.4 μg/mL for the tablet formulation and 20.1 ± 6.20 μg/mL for the suspension formulation and an average AUC0-LOQ of 156 (±76.1) h· μg/mL for the tablet formulation and 162 (±48.6) h· μg/mL for the suspension formulation. Relative bioavailability of the two oral formulations was 1.04 (suspension compared with tablet), whereas the absolute bioavailability of both oral formulations was estimated to be approximately 35–36% in the cross-study comparison with the i.v. pharmacokinetics. Combined with previous studies, these results suggest that a single daily oral dose of 5–10 mg  cefpodoxime/kg body weight as cefpodoxime proxetil maintains plasma concentrations effective for treatment of specified skin infections in dogs. [ABSTRACT FROM AUTHOR]

Maropitant is the first NK1 receptor antagonist developed to treat and prevent emesis in dogs; it is administered by subcutaneous (s.c.) injection at 1 mg/kg, or orally (p.o.), in tablet form, at either 2 or 8 mg/kg depending on indication. The absolute bioavailability of maropitant was markedly higher (90.7%) following s.c. injection than after oral administration (23.7% at the 2 mg/kg dose and 37.0% at the 8 mg/kg dose). First-pass metabolism contributes to the low bioavailability of maropitant following oral administration. The difference in bioavailability between the two oral doses reflects the nonlinear kinetics characterizing the disposition of maropitant within the 2–8 mg/kg dose range. Systemic clearance of maropitant following intravenous (i.v.) administration was 970, 995 and 533 mL/h·kg at doses of 1, 2 and 8 mg/kg, respectively. Nonproportional kinetics were observed for p.o. administered maropitant at doses ranging from 2 to 16 mg/kg but dose proportionality was demonstrated at higher doses (20–50 mg/kg). Linearity was also demonstrated following s.c. administration at 0.5, 1 and 2 mg/kg. Maximum plasma drug concentration ( Cmax) occurred 0.75 h ( tmax) after s.c. administration at 1 mg/kg, and at 1.7 and 1.9 h after oral administration of 8 and 2 mg/kg doses, respectively. The apparent terminal half-life of maropitant was 7.75, 4.03 and 5.46 h after dosing at 1 mg/kg (s.c.), 2 mg/kg (p.o.) and 8 mg/kg (p.o.), respectively. Feeding status had no effect on oral bioavailability. Limited accumulation occurred following once-daily administration of maropitant for five consecutive days at 1 mg/kg (s.c.) or 2 mg/kg (p.o.). At the dose of 8 mg/kg (p.o.) once daily for two consecutive days, the mean AUC0−24h (second dose) was 218% that of the first dose value. Urinary recovery of maropitant and its main metabolite was minimal (<1%), thus supporting the evidence that maropitant clearance is primarily hepatic. [ABSTRACT FROM AUTHOR]

The objectives of this study were to evaluate the effects of dirlotapide, a microsomal triglyceride transfer protein inhibitor, on apparent nutrient digestibility of an expanded dry dog food, on defecation frequency and fecal consistency. Eighteen beagles were randomized to either placebo ( n = 6) or dirlotapide ( n = 12). Testing was divided into a 21-day adaptation phase (days −21 to −1) and a 35-day treatment (digestibility testing) phase (days 0–35). During the treatment phase, dogs were administered oral dirlotapide (0.3 mg/kg) or placebo (0.06 mL/kg) once daily. For digestibility testing, feces were collected over two periods for 7 days each starting on days −9 and 28. All dogs were fed a commercial adult dog food throughout the study. Food intake was adjusted to maintain body weight during adaptation, followed by pair-feeding placebo dogs the amount of food ingested by the dirlotapide dogs during the treatment period. Dogs in both groups had reduced food intake and lost similar amounts of body weight during treatment. Dogs receiving 0.3 mg dirlotapide/kg once daily had a small but significant ( P = 0.018) decrease (6.16 ± 2.22%, mean ± SD) in crude fat digestibility compared with the placebo-treated food-restricted dogs, but no difference in crude protein, dry matter, or energy digestibility was observed. Fecal consistency and volume and defecation frequency were similar between groups. Dirlotapide effectively reduced appetite and energy intake without affecting nutrient digestibility, except for a minimal decrease in fat digestibility. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of cisplatin therapy. Maropitant (Cerenia™), a novel neurokinin-1 receptor antagonist, was evaluated for prevention and treatment of cisplatin-induced emesis in tumour-bearing dogs. Dogs ( n= 122) were randomly allocated to three treatment groups: T01, placebo before and after cisplatin; T02, placebo before and maropitant after cisplatin; or T03, maropitant before and placebo after cisplatin. Maropitant treatment (T02) following a cisplatin-induced-emetic event resulted in significantly fewer subsequent emetic events ( P= 0.0005) than in placebo-treated dogs (T01). In placebo-treated (T01) dogs, 56.4% were withdrawn from the study because of treatment failure compared with 5.3% in group T02. When maropitant was administered prior to cisplatin treatment (T03) in a prevention regime, 94.9% did not vomit compared with only 4.9% of placebo-treated dogs, and significantly fewer emetic events ( P < 0.0001) were observed in those dogs that did vomit. In summary, maropitant was safe and highly effective in reducing or completely preventing cisplatin-induced emesis. [ABSTRACT FROM AUTHOR]

Question: Do stressful environments facilitate plant invasion by providing refuges from intense above-ground competition associated with productive areas, or prevent it by favouring locally adapted native species? Location: An invaded and fragmented oak savanna ecosystem structured along a landscape-level stress gradient associated with soil depth, elevation, and canopy openness. Methods: Vegetation and environmental data were collected from 184 plots in seven savanna remnants along the gradient. Using multivariate (CCA) and post-hoc regression analyses, we determined the relationship between environment and the richness and abundance of invasives. Results: 46 of 119 species were naturalized exotics. CCA indicated the importance of environmental variation (mostly soil depth) for community structure but not for invasion; invasive species richness was similar in all areas. However, the abundance of invasives and their impacts on native diversity appear to increase significantly in less stressful habitats. Deeper soils had lower evenness and significantly fewer native species. This result was associated with dominance by exotic perennial grasses and large increases in vegetation height, suggesting strong above-ground competition. Conclusions: Low-stress environments were not more invasible per se but appear to be more susceptible to invasion by species with strong competitive impacts. The causes of decreasing exotic impact with decreasing soil depth may reflect shifts in competitive intensity or an increased importance of stress tolerance, both of which may favour natives. Alternatively, this ecosystem may simply lack high-impact invaders capable of dominating shallow soils. Conservation challenges are twofold for this endangered plant community: controlling invasives that currently dominate deeper-soils and accounting for a diverse pool of invaders that proliferate when the current dominants are removed. [ABSTRACT FROM AUTHOR]

Hibbard, B., Robb, E. J., Chester Jr., S. T., Dame, K. J., Boucher, J. F., Alaniz, G. R. Dose determination and confirmation of a long-acting formulation of Ceftiofur (Ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory disease. J. vet. Pharmacol. Therap. 25, 175–180. The objective of this work was to determine and confirm an effective dose of ceftiofur crystalline free acid sterile oil suspension (CCFA-SS, 100 mg ceftiofur equivalents (CE)/mL], a long-acting single-administration ceftiofur formulation, for the treatment of the bacterial component of bovine respiratory disease (BRD). Study 1 was a dose determination study that used an intratracheal Mannheimia haemolytica (Pasteurella haemolytica ) challenge model to evaluate single-administration doses of CCFA-SS at 0.0, 1.1, 2.2, 3.3, 4.4 or 5.5 mg CE/kg body weight (BW) for the treatment of BRD. Data from this study were used to select doses for field testing in three multi-location clinical studies. In Study 2, the efficacy of a single administration dose of CCFA-SS at 4.4 mg CE/kg BW was compared with a negative control for the treatment of naturally occurring BRD in feedlot cattle. Treatments were administered when uniform clinical signs of BRD were present. Study 3 used a design similar to Study 2, and compared single-administration doses of CCFA-SS at 3.0 or 4.4 mg CE/kg BW with the positive-control tilmicosin (Micotil® 300 Injection, Elanco Animal Health) at 10 mg/kg BW. Study 4 compared the efficacy of single doses of CCFA-SS of 1.1–8.8 mg CE/kg BW with tilmicosin at 10 mg/kg BW. A total of 1176 cattle were included in these clinical studies. In Study 1, a dose of 4.55 mg CE/kg BW was determined to be effective. This was rounded to 4.4 mg CE/kg for field testing. In Study 2, a single dose of CCFA-SS at 4.4 mg CE/kg BW had a higher treatment success rate on day 14 (61%) than negative controls (26%, P < 0.01). However, in Study... [ABSTRACT FROM AUTHOR]

The conversion to mucoid, exopolysaccharide alginate-overproducing phenotype in Pseudomonas aeruginosa during chronic respiratory infections in cystic fibrosis patients occurs via mutations that activate the alternative sigma factor AlgU (δ[sup E]). In this study, we demonstrate that conversion to mucoidy can be caused via a second, algU-independent pathway, in which alginate production and transcription of the critical algD promoter depend on another alternative δ factor, RpoN (δ [sup 54]). The algD promoters dependent on (δ[sup 54] and δ [sup E) showed a complete overlap resulting in identical mRNA 5′ ends. The two pathways were not independent, as (δ [sup 54] also repressed (δ[sup E]-dependent transcription of algD both in vitro and in vivo. The negative regulatory effect of (δ[sup 54] on δ [sup E]. dependent algD expression was based on δ[sup 54] binding to the algD promoter and its interference with δ[sup E]. dependent transcription. This phenomenon, referred to here as δ factor antagonism, reflects the unique properties of δ[sup 54], which lacks an intrinsic ability to form open transcription initiation complexes. We propose that this peculiar feature of δ[sup 54] has evolved in part to allow its recruitment as a repressor of certain promoter subsets. The repression of algD by δ[sup 54] also depends on environmental conditions, supporting the notion that δ factor antagonism plays a physiological role in controlling alginate production in P. aeruginosa during adaptation to different ecological sites (e.g. biofilm development, stress and other growth conditions) and unique environments in the chronically infected host. [ABSTRACT FROM AUTHOR]

It is well established that certain aspects of play in young children are related to their emerging linguistic skills. The present study examined the relationships between functional play, symbolic play, non-verbal ability, and expressive and receptive language in normally developing children aged between 1 and 6 years using standardized assessment procedures, including a recently developed Test of Pretend Play (ToPP). When effects of chronological age were partialled out, symbolic play remained significantly correlated with both expressive and receptive language, but not with functional play or non-verbal ability; and functional play was only correlated significantly with expressive language. It is concluded that ToPP will provide practitioners with a useful way of assessing symbolic ability in children between the ages of 1 and 6 years, and will contribute to the assessment and diagnosis of a number of communication difficulties, and have implications for intervention. [ABSTRACT FROM AUTHOR]

Five experiments are reported comparing metamemory abilities in children with autism, age- and language-matched mentally retarded children, and language-matched young normal controls. The mean language age of the participants in Experiment 1 was approximately 6 years, in Experiments 2, 3, and 4 approximately 8 years, and in Experiment 5 approximately 9 years. All the children were given one or more false belief tests. Experiment 1 assessed the children's understanding that a task variable (list length) and a person variable (age) will affect their own and others' performances on an immediate auditory-verbal recall task. Experiment 2 assessed the ability to utilize category cues in a picture recall task. Experiments 3 and 4 assessed the ability to verbalize strategies used in a memory span test and in one retrospective and two prospective memory situations. Experiment 5 assessed the children's knowledge and understanding of another person's memory. On the basis of available evidence and theory, we predicted that the children with autism would be impaired on all the metamemory tasks and that impairment would be associated with failure on tests of false belief. Our predictions were not supported. The children with autism were not impaired on any of the metamemory tasks, although they were less likely than controls to make spontaneous use of memory strategies involving other people. Unexpectedly few of the children failed the false belief tasks. These results are discussed in relation to theories concerning primary psychological deficits underlying autism. [ABSTRACT FROM AUTHOR]

Word learning depends critically on the use of linguistic context to constrain the likely meanings of words. However, the mechanisms by which children infer word meaning from linguistic context are still poorly understood. In this study, we asked whether adults (n = 58) and 2- to 6-year-old children (n = 180) use discourse coherence relations (i.e., the meaningful relationships between elements within a discourse) to constrain their interpretation of novel words. Specifically, we showed participants videos of novel animals exchanging objects. These videos were accompanied by a linguistic description of the events in which we manipulated a single word within a sentence (and vs. because) in order to alter the causal and temporal relations between the events in the discourse (e.g., "One animal handed the baby to the other animal [and/because] the baby started crying in the talfa's arms"). We then asked participants which animal (the giver or the receiver) was the referent of the novel word. Across two experiments, we found evidence that young children used the causal and temporal relations in each discourse to constrain their interpretations of novel words., (© 2019 Cognitive Science Society, Inc.)

Individuals with Williams syndrome (WS) show a specific deficit in visuo-spatial abilities. This finding, however, derives mainly from performance on small-scale laboratory-based tasks. This study investigated large-scale route learning in individuals with WS and two matched control groups (moderate learning difficulty group [MLD], typically developing group [TD]). In a non-labelling and a labelling (verbal information provided along the route) condition, participants were guided along one of two unfamiliar 1-km routes with 20 junctions, and then retraced the route themselves (two trials). The WS participants performed less well than the other groups, but given verbal information and repeated experience they learnt nearly all of the turns along the route. The extent of improvement in route knowledge (correct turns) in WS was comparable to that of the control groups. Relational knowledge (correctly identifying spatial relationships between landmarks), compared with the TD group, remained poor for both the WS and the MLD group. Assessment of the relationship between performance on the large-scale route-learning task and that on three small-scale tasks (maze learning, perspective taking, map use) showed no relationship for the TD controls, and only a few non-specific associations in the MLD and WS groups.

Autistic children were compared with age and ability matched controls on a test of immediate recall of word lists. Overall performance in the two groups was very similar. However, the overall recall scores were achieved differently by the two groups, the autistic subjects recalled significantly fewer earlier presented items and more later presented items than did controls. This finding is discussed in relation to the memory disabilities of adults suffering from the amnesic syndrome.

Autistic children were compared with control children on tasks in which retention was tested by different methods. In three tests of recall, using named pictures, written words and spoken words as test stimuli, autistic children were impaired in comparison with age-matched normal children and with controls matched for verbal ability. In one test of forced-choice recognition of pictures, autistic children were impaired in comparison with ability-matched controls. In three tests of cued recall, using named pictures, written words and spoken words as test stimuli, and acoustic, graphemic and semantic cues, autistic children were not impaired in comparison with normal age-matched controls. In one test of paired-associate learning using non-related word pairs as test stimuli autistic children were not impaired in comparison with normal age-matched controls. These experimental paradigms were similar to some that have been used to investigate the amnesic syndrome in man. Thus findings on paired-associate learning differ in autistic and amnesic subjects, but findings on recall, recognition and cued recall are comparable. A possible parallel between autism and amnesia is discussed.