Validation and standardisation of a two dimensional motion analysis technique to measure normal conformation and gait in Arabian horses.

The development of standardised two dimensional motion analysis techniques to obtain baseline measures would provide the equine industry with a consistent method for analysing equine conformation and gait. The use of these methods to define breed specific conformation and gait could be utilised by the industry for conformation and gait assessment. This study focussed on validating and standardising such methods to define normal conformation and gait for the Arabian horse. Validation involved comparing the accuracy of two 2D motion analysis software programmes; Quintic© and HU-M-AN (TM). Static and dynamic linear and angular validation was performed by comparing known values to values calculated by the software programmes. Higher variation was established for Quintic© measurements; the margin of error was up to 20mm for static measurements and 3.36° for angular measurements. When using Quintic©, angles of different size were measured with varying amounts of accuracy; these differences were significant (P0.05); the horses had breedspecific gait patterns which allowed normal gait to be defined for a distinct breed. A database of normal gait for the Arabian horse was created for use by Arab horse owners or breeders in the UK

Neuronal filopodia: From stochastic dynamics to robustness of brain morphogenesis

Brain development relies on dynamic morphogenesis and interactions of neurons. Filopodia are thin and highly dynamic membrane protrusions that are critically required for neuronal development and neuronal interactions with the environment. Filopodial interactions are typically characterized by non-deterministic dynamics, yet their involvement in developmental processes leads to stereotypic and robust outcomes. Here, we discuss recent advances in our understanding of how filopodial dynamics contribute to neuronal differentiation, migration, axonal and dendritic growth and synapse formation. Many of these advances are brought about by improved methods of live observation in intact developing brains. Recent findings integrate known and novel roles ranging from exploratory sensors and decision-making agents to pools for selection and mechanical functions. Different types of filopodial dynamics thereby reveal non-deterministic subcellular decision-making processes as part of genetically encoded brain development

War and deforestation in Sierra Leone

The impact of armed conflict on the environment is of major public policy importance. We use a geographically disaggregated dataset of civil war violence together with satellite imagery of land cover to test whether war facilitated or prevented forest loss in Sierra Leone. The conflict data set allows us to establish where rebel groups were stationed and where battles and attacks occurred. The satellite data enables to us to monitor the change in forest cover (total, primary, and secondary) in all of Sierra Leone's 151 chiefdoms, between 1990 (prior to the war) and 2000 (just prior to its end). The results suggest that conflict in Sierra Leone acted as a brake on local deforestation: conflict-ridden areas experienced significantly less forest loss relative to their more conflict-free counterparts

Zoonotic disease risk perceptions in the British veterinary profession

In human and veterinary medicine, reducing the risk of occupationally-acquired infections relies on effective infection prevention and control practices (IPCs). In veterinary medicine, zoonoses present a risk to practitioners, yet little is known about how these risks are understood and how this translates into health protective behaviour. This study aimed to explore risk perceptions within the British veterinary profession and identify motivators and barriers to compliance with IPCs. A cross-sectional study was conducted using veterinary practices registered with the Royal College of Veterinary Surgeons. Here we demonstrate that compliance with IPCs is influenced by more than just knowledge and experience, and understanding of risk is complex and multifactorial. Out of 252 respondents, the majority were not concerned about the risk of zoonoses (57.5%); however, a considerable proportion (34.9%) was. Overall, 44.0% of respondents reported contracting a confirmed or suspected zoonoses, most frequently dermatophytosis (58.6%). In veterinary professionals who had previous experience of managing zoonotic cases, time or financial constraints and a concern for adverse animal reactions were not perceived as barriers to use of personal protective equipment (PPE). For those working in large animal practice, the most significant motivator for using PPE was concerns over liability. When assessing responses to a range of different "infection control attitudes", veterinary nurses tended to have a more positive perspective, compared with veterinary surgeons. Our results demonstrate that IPCs are not always adhered to, and factors influencing motivators and barriers to compliance are not simply based on knowledge and experience. Educating veterinary professionals may help improve compliance to a certain extent, however increased knowledge does not necessarily equate to an increase in risk-mitigating behaviour. This highlights that the construction of risk is complex and circumstance-specific and to get a real grasp on compliance with IPCs, this construction needs to be explored in more depth

Within-subject comparison of near-death and psychedelic experiences: acute and enduring effects.

Mystical-like states of consciousness may arise through means such as psychedelic substances, but may also occur unexpectedly during near-death experiences (NDEs). So far, research studies comparing experiences induced by serotonergic psychedelics and NDEs, along with their enduring effects, have employed between-subject designs, limiting direct comparisons. We present results from an online survey exploring the phenomenology, attribution of reality, psychological insights, and enduring effects of NDEs and psychedelic experiences (PEs) in individuals who have experienced both at some point during their lifetime. We used frequentist and Bayesian analyses to determine significant differences and overlaps (evidence for null hypotheses) between the two. Thirty-one adults reported having experienced both an NDE (i.e. NDE-C scale total score ≥27/80) and a PE (intake of lysergic acid diethylamide, psilocybin/mushrooms, ayahuasca, N,N-dimethyltryptamine, or mescaline). Results revealed areas of overlap between both experiences for phenomenology, attribution of reality, psychological insights, and enduring effects. A finer-grained analysis of the phenomenology revealed a significant overlap in mystical-like effects, while low-level phenomena (sensory effects) were significantly different, with NDEs displaying higher scores of disembodiment and PEs higher scores of visual imagery. This suggests psychedelics as a useful model for studying mystical-like effects induced by NDEs, while highlighting distinctions in sensory experiences

Pets, Purity and Pollution: Why Conventional Models of Disease Transmission Do Not Work for Pet Rat Owners

In the United Kingdom, following the emergence of Seoul hantavirus in pet rat owners in 2012, public health authorities tried to communicate the risk of this zoonotic disease, but had limited success. To explore this lack of engagement with health advice, we conducted in-depth, semi-structured interviews with pet rat owners and analysed them using a grounded theory approach. The findings from these interviews suggest that rat owners construct their pets as different from wild rats, and by elevating the rat to the status of a pet, the powerful associations that rats have with dirt and disease are removed. Removing the rat from the contaminated outside world moves their pet rat from being ‘out of place’ to ‘in place’. A concept of ‘bounded purity’ keeps the rat protected within the home, allowing owners to interact with their pet, safe in the knowledge that it is clean and disease-free. Additionally, owners constructed a ‘hierarchy of purity’ for their pets, and it is on this structure of disease and risk that owners base their behaviour, not conventional biomedical models of disease

Microdialysis of Drug and Drug Metabolite: a Comprehensive In Vitro Analysis for Voriconazole and Voriconazole N-oxide

Purpose Voriconazole is a therapeutically challenging antifungal drug associated with high interindividual pharmacokinetic variability. As a prerequisite to performing clinical trials using the minimally-invasive sampling technique microdialysis, a comprehensive in vitro microdialysis characterization of voriconazole (VRC) and its potentially toxic N-oxide metabolite (NO) was performed. Methods The feasibility of simultaneous microdialysis of VRC and NO was explored in vitro by investigating the relative recovery (RR) of both compounds in the absence and presence of the other. The dependency of RR on compound combination, concentration, microdialysis catheter and study day was evaluated and quantified by linear mixed-effects modeling. Results Median RR of VRC and NO during individual microdialysis were high (87.6% and 91.1%). During simultaneous microdialysis of VRC and NO, median RR did not change (87.9% and 91.1%). The linear mixed-effects model confirmed the absence of significant differences between RR of VRC and NO during individual and simultaneous microdialysis as well as between the two compounds (p > 0.05). No concentration dependency of RR was found (p = 0.284). The study day was the main source of variability (46.3%) while the microdialysis catheter only had a minor effect (4.33%). VRC retrodialysis proved feasible as catheter calibration for both compounds. Conclusion These in vitro microdialysis results encourage the application of microdialysis in clinical trials to assess target-site concentrations of VRC and NO. This can support the generation of a coherent understanding of VRC pharmacokinetics and its sources of variability. Ultimately, a better understanding of human VRC pharmacokinetics might contribute to the development of personalized dosing strategies

Microdialysis of Voriconazole and its N-Oxide Metabolite: Amalgamating Knowledge of Distribution and Metabolism Processes in Humans

Purpose Voriconazole is an essential antifungal drug whose complex pharmacokinetics with high interindividual variability impedes effective and safe therapy. By application of the minimally-invasive sampling technique microdialysis, interstitial space fluid (ISF) concentrations of VRC and its potentially toxic N-oxide metabolite (NO) were assessed to evaluate target-site exposure for further elucidating VRC pharmacokinetics. Methods Plasma and ISF samples of a clinical trial with an approved VRC dosing regimen were analyzed for VRC and NO concentrations. Concentration-time profiles, exposure assessed as area-under-the-curve (AUC) and metabolic ratios of four healthy adults in plasma and ISF were evaluated regarding the impact of multiple dosing and CYP2C19 genotype. Results VRC and NO revealed distribution into ISF with AUC values being ≤2.82- and 17.7-fold lower compared to plasma, respectively. Intraindividual variability of metabolic ratios was largest after the first VRC dose administration while interindividual variability increased with multiple dosing. The CYP2C19 genotype influenced interindividual differences with a maximum 6- and 24-fold larger AUCNO/AUCVRC ratio between the intermediate and rapid metabolizer in plasma and ISF, respectively. VRC metabolism was saturated/auto-inhibited indicated by substantially decreasing metabolic concentration ratios with increasing VRC concentrations and after multiple dosing. Conclusion The feasibility of the simultaneous microdialysis of VRC and NO in vivo was demonstrated and provided new quantitative insights by leveraging distribution and metabolism processes of VRC in humans. The exploratory analysis suggested substantial dissimilarities of VRC and NO pharmacokinetics in plasma and ISF. Ultimately, a thorough understanding of target-site pharmacokinetics might contribute to the optimization of personalized VRC dosing regimens

Adjunctive interferon-γ immunotherapy for the treatment of HIV-associated cryptococcal meningitis: a randomized controlled trial.

BACKGROUND: Interferon-gamma (IFNγ) is of key importance in the immune response to Cryptococcus neoformans. Mortality related to cryptococcal meningitis remains high, and novel treatment strategies are needed. We performed a randomized controlled trial to determine whether addition of IFNγ to standard therapy increased the rate of clearance of cryptococcal infection in HIV-associated cryptococcal meningitis. METHODS: Patients were randomized to amphotericin B 1 mg/kg per day and 5FC 100 mg/kg per day for 2 weeks (standard therapy), standard therapy and IFNγ1b 100 μg days 1 and 3 (IFNγ two doses), or standard therapy and IFNγ1b 100 μg days 1, 3, 5, 8, 10 and 12 (IFNγ six doses). Primary outcome was rate of clearance of cryptococcus from the cerebrospinal fluid (CSF) (early fungicidal activity, EFA) calculated from serial quantitative cultures, previously shown to be independently associated with survival. RESULTS: Rate of fungal clearance was significantly faster in IFNγ containing groups than with standard treatment. Mean EFA [log colony forming unit (CFU)/ml per day] was -0.49 with standard treatment, -0.64 with IFNγ two doses, and -0.64 with IFNγ six doses. Difference in EFA was -0.15 [confidence interval (95% CI) -0.02 to -0.27, P=0.02] between standard treatment and IFNγ two doses, and -0.15 (95% CI -0.05 to -0.26, P=0.006) between standard treatment and IFNγ six doses. Mortality was 16% (14/88) at 2 weeks and 31% (27/87) at 10 weeks, with no significant difference between groups. All treatments were well tolerated. CONCLUSION: Addition of short-course IFNγ to standard treatment significantly increased the rate of clearance of cryptococcal infection from the CSF, and was not associated with any increase in adverse events. Two doses of IFNγ are as effective as six doses