Neural correlates involved in perspective-taking in early childhood.

Learning to consider another person's perspective is pivotal in early social development. Still, little is known about the neural underpinnings involved in perspective-taking in early childhood. In this EEG study, we examined 4-year-old children's brain activity during a live, social interaction that involved perspective-taking. Children were asked to pass one of two toys to another person. To decide which toy to pass, they had to consider either their partner's perspective (perspective-taking) or visual features unrelated to their partner's perspective (control). We analyzed power changes in midfrontal and temporal-parietal EEG channels. The results indicated that children showed higher power around 7 Hz at right temporal-parietal channels for perspective-taking compared to control trials. This power difference was positively correlated with children's perspective-taking performance, specifically for trials in which they needed to pass the toy their partner could not see. A similar power difference at right temporal-parietal channels was seen when comparing perspective-taking trials where children's visual access mismatched rather than matched that of their partner. No differences were detected for midfrontal channels. In sum, we identified distinct neural activity as 4-year-olds considered another person's perspective in a live interaction; this activity converges with neural findings of adults' social processing network.

Water consumption and wastage behaviour in pigs: implications for antimicrobial administration and stewardship.

Daily water use and wastage patterns of pigs have major effects on the efficacy of in-water antimicrobial dosing events when conducted for metaphylaxis or to treat clinical disease. However, daily water use and wastage patterns of pigs are not routinely quantified on farms and are not well understood. We conducted a prospective, observational 27-day study of the daily water use and wastage patterns of a pen group of 15 finisher pigs reared in a farm building. We found that the group of pigs wasted a median of 36.5% of the water used per day. We developed models of the patterns of water used and wasted by pigs over each 24-h period using a Bayesian statistical method with the brm() function in the brms package. Both patterns were uni-modal, peaking at 1400-1700, and closely aligned. Wastage was slightly greater during hours of higher water use. We have shown that it is feasible to quantify the water use and wastage patterns of pigs in farm buildings using a system that records and aggregates data, and analyses them using hierarchical generalised additive models. This system could support more efficacious in-water antimicrobial dosing on farms, and better antimicrobial stewardship, by helping to reduce the quantities of antimicrobials used and disseminated into the environment.

Observations on the use of a pain numbing device for repetitive percutaneous sampling in sheep.

AIMS: To evaluate the success of a commercially available analgesic device (CoolSense; Coolsense Ltd, Tel Aviv, Israel) in ameliorating pain while sampling from subcutaneous tissue cages in sheep. METHODS: The CoolSense device was used as part of a major parent study involving repetitive percutaneous sampling of subcutaneous tissue cages in seven sheep. Sampling was performed by passing a hypodermic needle through the skin and withdrawing fluid from the tissue cage. Each sheep had 10 tissue cages that were individually sampled 14 times over 74 h. The device was placed on the skin of the sampling site immediately before sampling cooling and numbing the skin. The reaction of the sheep was observed by the operators, flinching or jumping as the needle was passed through the skin was deemed to be a failure. We recorded the success or failure of the device for each needle stick. This was opportunistic data collection as part of a pharmacokinetic trial, therefore no controls were included. RESULTS: A total of 1655 observations were recorded and then analysed using a generalised linear mixed model. Overall, 1380 of 1655 (83.4%) observations were recorded as successfully providing analgesia. Marked inter-occasion variability was noted with success ranging from 61.42% to 92.86% across sheep:period (approximately 140 observations each). As no controls were available, the effect of treatment could not be evaluated. CONCLUSIONS AND CLINICAL RELEVANCE: The CoolSense device is a viable option for veterinary research and clinical applications.

Assessment of the clinical usefulness of ultrasound-guided cytological specimens obtained from gastrointestinal lesions in dogs and cats.

OBJECTIVES: Cytological biopsies are an integral additional test to an abdominal ultrasound when a lesion is identified, but there is little published on factors that that may impact achieving a clinically useful sample of gastrointestinal lesions obtained by ultrasound-guided fine-needle cytologic biopsy. This retrospective, descriptive study aimed to assess factors that may influence the clinical usefulness of submitted cytological samples collected from gastrointestinal lesions by ultrasound-guided percutaneous fine-needle cytologic biopsy. MATERIAL AND METHODS: Gastrointestinal cytological samples obtained from 25 dogs and 19 cats over 2.5 years were reviewed and determined as clinically useful or clinically useless as per the cytology report. Variables dependent on the ultrasound exam that were used in the analysis included lesion location, lesion thickness, loss of gastrointestinal layering, and the number of slides submitted. RESULTS: Thirty (30/44) of the submitted cytological samples were considered clinically useful. Factors associated with achieving a clinically useful sample in univariable models included the number of slides submitted and the thickness of the lesion. However, these two variables appear inter-related, as a weak correlation existed between them. Where histologic biopsies were obtained, a clinically useful sample had a partial or complete agreement with histology in three of 12 and eight of 12 cases, respectively. CLINICAL SIGNIFICANCE: Ultrasound-guided fine-needle cytological biopsies of gastrointestinal masses provided a clinically useful sample in two-third of the cases, especially if more slides were provided to the cytologist and thicker lesions were sampled.

Population physiologically based modeling of pirlimycin milk concentrations in dairy cows.

Predictions of drug residues in milk are critical in food protection and are a major consideration in the economics of treatment of mastitis in dairy cows. Nonlinear mixed-effects modeling (NLME) has been advocated as a suitable pharmaco-statistical method for the study of drug residues in milk. Recent developments in physiologically based pharmacokinetic (PBPK) modeling of intramammary drugs allow the combination of a mechanistic description of milk pharmacokinetics with NLME methods. The PBPK model was applied to NLME analysis of a data set consisting of milk drug concentrations from 78 healthy cows and 117 with clinical mastitis. Pirlimycin milk pharmacokinetics were adequately described by the model across the range of observed concentrations. Mastitis was characterized by increased variance in milk production volume. Udder residual volume was larger in cows with 1, or 2 or greater diseased mammary glands than in the healthy cows. Low-producing cows had a greater risk of prolonged milk residues. With the exclusion of the low-production cows, the model predicted that healthy cows required a milk discard time 12 h longer than that indicated by the label, and the diseased cows 36 h longer than indicated by the label. More pirlimycin was systemically absorbed in the gram-positive infected compared with the gram-negative infected or healthy cows, suggesting a greater risk of violative meat residues in gram-positive infected cows. Using NLME and PBPK models, we identified factors associated with changes in pirlimycin milk residues that may affect food safety. This model extends the verification of a simple physiologically based framework for the study of intramammary drugs.

Survival time and relapse in dogs with meningoencephalomyelitis of unknown origin treated with prednisolone and ciclosporin: a retrospective study.

OBJECTIVE: To analyse outcome in dogs with a presumptive diagnosis of meningoencephalomyelitis of unknown origin (MUO) treated with prednisolone and ciclosporin and to assess the effect of a number of patient variables on survival time and rate of relapse. DESIGN: Retrospective case series. METHODS: Medical records of 40 client-owned dogs with a diagnosis of MUO treated with prednisolone and ciclosporin at one institution between June 2010 and January 2018 were reviewed retrospectively to assess survival times and prognostic indicators for death and/or relapse. The minimum follow-up time was 11 months post-diagnosis. RESULTS: Median survival was 1345 days (95% confidence interval: 487-∞). No associations with hazard of death or relapse were detected for the presence of multifocal magnetic resonance imaging (MRI) abnormalities, caudal fossa location of MRI abnormalities, value of cerebrospinal fluid total nucleated cell count or total protein at time of diagnosis, or suspected elevation in intracranial pressure at time of diagnosis. CONCLUSION: Protracted survival time may be achieved with a treatment combination of prednisolone and ciclosporin. Suspected elevation in intracranial pressure at the time of diagnosis did not affect long-term outcome in this cohort.

Breed is associated with the ABCB1-1Δ mutation in Australian dogs.

OBJECTIVE: The ABCB1 gene encodes P-glycoprotein (P-gp), a cellular membrane pump. One functional mutation that leads to expression of a less functional form of P-gp, ABCB1-1Δ, has been described in dogs. Individuals with this mutation can have severe adverse reactions to common veterinary pharmaceuticals that are known substrates of this pump. We investigated the detection of this mutation in samples submitted to two Australian diagnostic laboratories. METHODS: A total of 4842 dogs across 27 breeds were tested for the ABCB1-1Δ mutation from buccal swabs or EDTA blood using standard PCR, multiplex PCR, or genotyping chip. Statistical analysis was applied to determine the proportions and odds ratios of the ABCB1-1Δ mutation in herding breeds compared with non-herding breeds. RESULTS: The ABCB1-1Δ mutation was detected in nine breeds. The most commonly affected breeds were collies, Australian shepherds, white Swiss shepherds, and Shetland sheepdogs. Of 32 dogs in 18 non-herding breeds tested, one cocker spaniel and one labradoodle were positive for the mutation, both heterozygous. CONCLUSION: The most frequently affected breeds for ABCB1-1Δ mutation are the collie, Australian shepherd, white Swiss shepherd and Shetland sheepdog. As the mutation is associated with an increased incidence of adverse reactions to commonly used pharmaceuticals, veterinarians need to be aware of the breeds at most risk of carrying this mutation and consider testing these individuals prior to administering these medications.

The burden of mental disorders and access to mental health and psychosocial support services in Syria and among Syrian refugees in neighboring countries: a systematic review.

BACKGROUND: Exposure to conflict, violence and forced displacement can increase poor mental health among affected populations. Our aim was to examine evidence on the burden of mental disorders and access to and effectiveness of mental health and psychosocial support (MHPSS) services in Syria and among Syrian refugees in neighboring countries. METHODS: A systematic review was done following systematic review criteria. Twelve bibliographic databases and additional gray literature sources were searched for quantitative and qualitative studies. Descriptive analysis and quality assessment were conducted. RESULTS: Twenty-eight eligible studies were identified, of which two were with conflict-affected populations within Syria. Levels of post-traumatic stress disorder ranged from 16 to 84%, depression from 11 to 49%, and anxiety disorder from 49 to 55%. Common risk factors were exposures to trauma and having a personal or family history of mental disorder. Financial and socio-cultural barriers were identified as the main obstacles to accessing MHPSS care. Evaluations of MHPSS services, albeit from predominantly nonrandomised designs, reported positive treatment outcomes. CONCLUSIONS: The MHPSS burden was high, but with considerable variation between studies. There are key evidence gaps on: MHPSS burden and interventions-particularly for those living within Syria; access and barriers to care; and implementation and evaluation of MHPSS interventions.

Review: Water medication of growing pigs: sources of between-animal variability in systemic exposure to antimicrobials.

On many Australian commercial pig farms, groups of growing pigs are mass-medicated through their drinking water with selected antimicrobials for short periods to manage herd health. However, delivery of medication in drinking water cannot be assumed to deliver an equal dose to all animals in a group. There is substantial between-animal variability in systemic exposure to an antimicrobial (i.e. the antimicrobial concentration in plasma), resulting in under-dosing or over-dosing of many pigs. Three sources of this between-animal variability during a water medication dosing event are differences in: (1) concentration of the active constituent of the antimicrobial product in water available to pigs at drinking appliances in each pen over time, (2) medicated water consumption patterns of pigs in each pen over time, and (3) pharmacokinetics (i.e. oral bioavailability, volume of distribution and clearance between pigs and within pigs over time). It is essential that factors operating on each farm that influence the range of systemic exposures of pigs to an antimicrobial are factored into antimicrobial administration regimens to reduce under-dosing and over-dosing.

Generation of a series of Bn fused oligo-naphthalenes (n = 1 to 3) from a B1-polycyclic aromatic hydrocarbon.

A series of Bn-PAHs have been prepared by functionalisation of a B1-PAH, leading to the first only boron doped B3-PAH to the best of our knowledge. These Bn-PAHs represent the first three members of a series of {B-Mes} fused oligo-naphthalenes and trends in key properties of this series have been elucidated.

Controlled before-after intervention study of suburb-wide street changes to increase walking and cycling: Te Ara Mua-Future Streets study design.

BACKGROUND: Achieving a shift from car use to walking, cycling and public transport in cities is a crucial part of healthier, more environmentally sustainable human habitats. Creating supportive active travel environments is an important precursor to this shift. The longevity of urban infrastructure necessitates retrofitting existing suburban neighbourhoods. Previous studies of the effects of street changes have generally relied on natural experiments, have included few outcomes, and have seldom attempted to understand the equity impacts of such interventions. METHODS: In this paper we describe the design of Te Ara Mua - Future Streets, a mixed-methods, controlled before-after intervention study to assess the effect of retrofitting street changes at the suburb scale on multiple health, social and environmental outcomes. The study has a particular focus on identifying factors that improve walking and cycling to local destinations in low-income neighbourhoods and on reducing social and health inequities experienced by Maori (Indigenous New Zealanders) and Pacific people. Qualitative system dynamics modelling was used to develop a causal theory for the relationships between active travel, and walking and cycling infrastructure. On this basis we selected outcomes of interest. Together with the transport funder, we triangulated best evidence from the literature, transport policy makers, urban design professionals and community knowledge to develop interventions that were contextually and culturally appropriate. Using a combination of direct observation and random sample face to face surveys, we are measuring outcomes in these domains of wellbeing: road-user behaviour, changes to travel mode for short trips, physical activity, air quality, road traffic injuries, greenhouse gas emissions, and perceptions of neighbourhood social connection, safety, and walking and cycling infrastructure . DISCUSSION: While building on previous natural experiments, Te Ara Mua - Future Streets is unique in testing an intervention designed by the research team, community and transport investors together; including a wide range of objective outcome measures; and having an equity focus. When undertaking integrated intervention studies of this kind, a careful balance is needed between epidemiological imperatives, the constraints of transport funding and implementation and community priorities, while retaining the ability to contribute new evidence for healthy, equitable transport policy. The study was retrospectively registered as a clinical trial on 21 June 2018 in the ISCRTN registry: ISRCTN89845334 http://www.isrctn.com/ISRCTN89845334.

Clinical safety of percutaneous ultrasound-guided fine-needle aspiration of adrenal gland lesions in 19 dogs.

OBJECTIVE: To evaluate the safety of fine-needle aspiration of adrenal gland lesions in dogs and to characterise the risks in a subset of patients with cytologically or histopathologically diagnosed phaeochromocytoma. MATERIALS AND METHODS: Retrospective review of medical records of dogs that underwent percutaneous ultrasound-guided fine-needle aspiration of adrenal gland lesions between August 2014 and December 2016. Nineteen dogs were identified, with three undergoing bilateral adrenal gland aspiration and one dog undergoing aspiration twice, yielding 23 cytology samples in total. Data collected included signalment, concurrent medical conditions, current medications, blood pressure and heart rate before adrenal fine-needle aspiration, imaging characteristics of the adrenal gland lesions and any clinically apparent procedure-related complications. RESULTS: Phaeochromocytoma was diagnosed in nine of 19 dogs, including one dog with bilateral phaeochromocytoma. One dog developed ventricular tachycardia following aspiration of an adrenal gland lesion cytologically consistent with a phaeochromocytoma. CLINICAL SIGNIFICANCE: Percutaneous ultrasound-guided fine-needle aspiration of adrenal gland lesions appears to be relatively safe, even in phaeochromocytoma, but further data are required to lend more weight to this finding. Minimally invasive aspirates could be considered as part of the diagnostic algorithm in the investigation of an incidentally detected adrenal gland lesion of uncertain clinical significance.

Impact of beta-blockers on cardiopulmonary exercise testing in patients with advanced liver disease.

BACKGROUND: Patients with advanced liver disease may develop portal hypertension that can result in variceal haemorrhage. Beta-blockers reduce portal pressure and minimise haemorrhage risk. These medications may attenuate measures of cardiopulmonary performance, such as the ventilatory threshold and peak oxygen uptake measured via cardiopulmonary exercise testing. AIM: To determine the effect of beta-blockers on cardiopulmonary exercise testing variables in patients with advanced liver disease. METHODS: This was a cross-sectional analysis of 72 participants who completed a cardiopulmonary exercise test before liver transplantation. All participants remained on their usual beta-blocker dose and timing prior to the test. Variables measured during cardiopulmonary exercise testing included the ventilatory threshold, peak oxygen uptake, heart rate, oxygen pulse, the oxygen uptake efficiency slope and the ventilatory equivalents for carbon dioxide slope. RESULTS: Participants taking beta-blockers (n = 28) had a lower ventilatory threshold (P <.01) and peak oxygen uptake (P = .02), compared to participants not taking beta-blockers. After adjusting for age, the model of end-stage liver-disease score, liver-disease aetiology, presence of refractory ascites and ventilatory threshold remained significantly lower in the beta-blocker group (P = .04). The oxygen uptake efficiency slope was not impacted by beta-blocker use. CONCLUSIONS: Ventilatory threshold is reduced in patients with advanced liver disease taking beta-blockers compared to those not taking the medication. This may incorrectly risk stratify patients on beta-blockers and has implications for patient management before and after liver transplantation. The oxygen uptake efficiency slope was not influenced by beta-blockers and may therefore be a better measure of cardiopulmonary performance in this patient population.

The cardiopulmonary effects and quality of anesthesia after induction with alfaxalone in 2-hydroxypropyl-ß-cyclodextrin in dogs and cats: a systematic review.

To systematically review the quality of evidence comparing the cardiopulmonary effects and quality of anesthesia after induction with alfaxalone vs. other anesthetic agents in dogs and cats. Studies published from 2001 until 20th May 2013 were identified with the terms 'alfaxan' OR 'alfaxalone' OR 'alphaxalone' in electronic databases: Discovery, PubMed, ScienceDirect, and Wiley Interscience. The study design and risk of bias of all included studies were assessed. Twenty-two studies from 408 (22 of 408, 5.39%) satisfied the inclusion criteria. Fourteen studies (14 of 22, 64%) focused on dogs and nine (9 of 22, 40%) on cats. One study had both dogs and cats as subjects. (Hunt et al., 2013) Twelve studies were rated an LOE1, and six of these as ROB1. One, seven, and two studies were rated as LOE2, LOE3, and LOE5, respectively. In dogs, strong evidence shows that induction quality with either alfaxalone-HPCD or propofol is smooth. Moderate evidence supports this finding in cats. In dogs, moderate evidence shows that there is no significant change in heart rate after induction with either alfaxalone-HPCD or propofol. In cats, moderate evidence shows no significant difference in postinduction respiratory rate and heart rate between alfaxalone-HPCD and propofol induction. Strong evidence shows dogs and cats have smooth recoveries after induction using either alfaxalone-HPCD or propofol, before reaching sternal recumbency.

Ultrafast spectroscopy, superluminescence and theoretical modeling of a two-photon absorbing fluorene derivative.

A comprehensive study of photophysical and photochemical properties of an unsymmetrical fluorene derivative is presented, including linear absorption, fluorescence excitation anisotropy, photochemical stability, steady-state fluorescence, and fluorescence lifetimes in organic solvents of different polarities. Nonlinear optical properties were investigated using Z-scan measurements of degenerate two-photon absorption and femtosecond pump-probe spectroscopy. The strongly fluorescent compound exhibited good photostability, positioning it for use in a number of applications. A dramatic increase in fluorescence intensity along with spectral narrowing was observed under femtosecond pumping, demonstrating amplified spontaneous emission. An extensive set of experimental data is rationalized based on essential state models.

Pharmacokinetics of enrofloxacin following oral and subcutaneous administration in the common ringtail possum (Pseudocheirus peregrinus).

[Correction added on 23 March 2015, after first online publication: Terminal half-life values of enrofloxacin is corrected in the fourth sentence of the abstract] Clinically healthy common ringtail possums (n = 5) received single doses of 10 mg/kg enrofloxacin orally and then 2 weeks later subcutaneously. Serial plasma samples were collected over 24 h for each treatment phase, and enrofloxacin concentrations were determined using a validated HPLC assay. Pharmacokinetic parameters were determined by noncompartmental analysis. Following oral administration, plasma concentrations were of therapeutic relevance (Cmax median 5.45 µg/mL, range 2.98-6.9 µg/mL), with terminal-phase half-life (t½ ) shorter than in other species (median 3.09 h, range 1.79-5.30 h). In contrast, subcutaneous administration of enrofloxacin did not achieve effective plasma concentrations, with plasma concentrations too erratic to fit the noncompartmental model except in one animal. On the basis of the AUC:MIC, enrofloxacin administered at 10 mg/kg orally, but not subcutaneously, is likely to be effective against a range of bacterial species that have been reported in common ringtail possums.

In vitro sensitivity of the amphibian pathogen Batrachochytrium dendrobatidis to antifungal therapeutics.

Chytridiomycosis, a skin disease caused by Batrachochytrium dendrobatidis, has caused amphibian declines worldwide. Amphibians can be treated by percutaneous application of antimicrobials, but knowledge of in vitro susceptibility is lacking. Using a modified broth microdilution method, we describe the in vitro sensitivity of two Australian isolates of B. dendrobatidis to six antimicrobial agents. Growth inhibition was observed, by measurement of optical density, with all agents. Minimum inhibitory concentrations (µg/ml; isolate 1/2) were - voriconazole 0.016/0.008; itraconazole 0.032/0.016; terbinafine 0.063/0.063; fluconazole 0.31/0.31; chloramphenicol 12.5/12.5; amphotericin B 12.5/6.25. Killing effects on zoospores were assessed by observing motility. Amphotericin B and terbinafine killed zoospores within 5 and 30 min depending on concentration, but other antimicrobials were not effective at the highest concentrations tested (100 µg/ml). This knowledge will help in drug selection and treatment optimization. As terbinafine was potent and has rapid effects, study of its pharmacokinetics, safety and efficacy is recommended.

Chilaiditi's syndrome associated with colonic volvulus and intestinal malrotation-A rare case.

INTRODUCTION: Chilaiditi's syndrome (symptomatic hepatodiaphragmatic interposition of the colon) is an exceptionally rare cause of bowel obstruction and may present difficulty in diagnosis and management. This is the first reported case of colonic volvulus occurring in Chilaiditi's syndrome in association with intestinal malrotation and this case study describes its successful management. PRESENTATION OF CASE: An 18 year old male presented as an emergency with vague abdominal pain and a past history of gastroschisis repair with intestinal malrotation. CT scanning showed a closed loop obstruction due to a volvulus of the colon herniating under the falciform ligament. The patient was successfully treated by surgical reduction of the hernia, anatomical correction of the malrotation and caecopexy with a tube caecostomy. At six month follow up the patient was well and asymptomatic. DISCUSSION: In nine of the previously reported cases of Chilaiditi's syndrome with colonic volvulus, treatment was by partial colonic resection of which a third underwent stoma formation. One patient died as a consequence of anastomotic leak following primary anastomosis. We therefore suggest an alternative approach to management. CONCLUSION: Chilaiditi's syndrome with colonic volvulus in association with intestinal malrotation has not previously been described. As there is no consensus in the literature as to how to manage such a case we suggest that reduction of the volvulus, anatomical correction of the malrotation and fixation of the caecum by tube caecostomy results in a successful outcome. This approach avoids the need for colonic resection and possible stoma formation.

Binding of transmembrane mucins to galectin-3 limits herpesvirus 1 infection of human corneal keratinocytes.

Epithelial cells lining mucosal surfaces impose multiple barriers to viral infection. At the ocular surface, the carbohydrate-binding protein galectin-3 maintains barrier function by cross-linking transmembrane mucins on the apical glycocalyx. Despite these defense mechanisms, many viruses have evolved to exploit fundamental cellular processes on host cells. Here, we use affinity assays to show that herpes simplex virus type 1 (HSV-1), but not HSV-2, binds human galectin-3. Knockdown of galectin-3 in human corneal keratinocytes by small interfering RNA significantly impaired HSV-1 infection, but not expression of nectin-1, indicating that galectin-3 is a herpesvirus entry mediator. Interestingly, exposure of epithelial cell cultures to transmembrane mucin isolates decreased viral infectivity. Moreover, HSV-1 failed to elute the biological counterreceptor MUC16 from galectin-3 affinity columns, suggesting that association of transmembrane mucins to galectin-3 provides protection against viral infection. Together, these results indicate that HSV-1 exploits galectin-3 to enhance virus attachment to host cells and support a protective role for transmembrane mucins under physiological conditions by masking viral entry mediators on the epithelial glycocalyx.