Face Value: Remote facial expression analysis adds predictive power to perceived effectiveness for selecting anti-tobacco PSAs.

Perceived effectiveness (PE) is a validated tool for predicting the potential impact of anti-tobacco public service announcements (PSAs). We set out to evaluate the added predictive value of facial expression analysis when combined with PE in a remote (online) survey. Each of 302 tobacco users watched 3 PSAs and allowed transmission of webcam videos from which metrics for "attention" (head position) and "facial action units" (FAU) were computed. The participants completed scales for their subjective emotions, willingness to share on social media, and intention to quit smoking using the Tobacco Free Florida website. Based on PE, both ready to quit (RTQ) and not ready (NR) respondents favored the same PSAs but RTQs assigned higher PE scores. Negative PSAs ("sad" or "frightening") were more compelling overall but RTQs also favored surprising ads and were more willing to share them on social media. Logistic regression showed that the combination of Attention + FAU+ PE (AUC = .816, p < .0001) outperformed single factors or factor combinations in distinguishing RTQ from NR. This study demonstrates that on-line assessment of facial expressions enhances the predictive value of PE and can be deployed on large remote samples.

3D characterisation of dry powder inhaler formulations: Developing X-ray micro computed tomography approaches.

Carrier-based dry powder inhaler (DPI) formulations need to be accurately characterised for their particle size distributions, surface roughnesses, fines contents and flow properties. Understanding the micro-structure of the powder formulation is crucial, yet current characterisation methods give incomplete information. Commonly used techniques like laser diffraction (LD) and optical microscopy (OM) are limited due to the assumption of sphericity and can give variable results depending on particle orientation and dispersion. The aim of this work was to develop new three dimensional (3D) powder analytical techniques using X-ray computed tomography (XCT) that could be employed for non-destructive metrology of inhaled formulations. α-lactose monohydrate powders with different characteristics have been analysed, and their size and shape (sphericity/aspect ratio) distributions compared with results from LD and OM. The three techniques were shown to produce comparable size distributions, while the different shape distributions from XCT and OM highlight the difference between 2D and 3D imaging. The effect of micro-structure on flowability was also analysed through 3D measurements of void volume and tap density. This study has demonstrated for the first time that XCT provides an invaluable, non-destructive and analytical approach to obtain number- and volume-based particle size distributions of DPI formulations in 3D space, and for unique 3D characterisation of powder micro-structure.

A new method for determining levels of sedation in dogs: A pilot study with propofol and a novel neuroactive steroid anesthetic.

BACKGROUND: Different levels of consciousness are required in order to perform different medical procedures. Sedation scales established to objectively define various levels of sedation in humans have not been thoroughly characterized in non-human species. Postural changes in rats or dogs are useful as gross measures of sedation but are inadequate for quantitative assessment since graded levels of sedation are difficult to delineate and obscured by movement abnormalities. NEW METHOD: A new canine sedation scoring (CSS) method was developed based on the modified observer's assessment of alertness and sedation score (MOAA/S) used in humans. The method employed a combination of physical, auditory and somatosensory stimuli of increasing intensity. Cardiovascular, respiratory, and a neurophysiological measure of sedation (bispectral index: BIS) data were recorded. Validation studies were performed following intravenous loading and constant rate infusion of propofol or a novel synthetic neuroactive steroid (SGE-746). RESULTS: Four levels of consciousness were identified: 1) Awake, 2) Moderate Sedation (MS), 3) Deep Sedation (DS) and 4) General Anesthesia (GA). Cardiorespiratory measurements obtained after bolus administration of propofol and SGE-746 and at the end of each CRI remained within normal limits. Canine sedation scores correlated with BIS for SGE-746. SGE-746 exhibited a more gradual exposure-response relationship than propofol. Larger increases in the plasma concentration from awake values were required to achieve different levels of sedation with SGE-746 compared to propofol. COMPARISON WITH EXISTING METHODS: No other canine sedation scoring methods are widely accepted. CONCLUSION: A CSS method, based on the human MOAA/S scale defined four levels of consciousness in dogs and provided better resolution of sedation depth than BIS alone.

Examination of inequivalent wetting on the crystal habit surfaces of RS-ibuprofen using grid-based molecular modelling.

Synthonic engineering tools, including grid-based searching molecular modelling, are applied to investigate the wetting interactions of the solute and four crystallisation solvents (ethanol, ethyl acetate, acetonitrile and toluene) with the {100}, {001} and {011} forms of RS-ibuprofen. The grid-based methods, in particular the construction of a crystal slab parallel to a given plane in a coordinate system with one axis perpendicular to the surface, are defined in detail. The interaction strengths and nature (dispersive, hydrogen bonding (H-bonding) or coulombic forces) are related to the crystal growth rates and morphologies. The solute is found to interact strongest with the capping {011}, then the side {001} and weakest with the top {100} habit surfaces. The solute interactions with the {100} and {001} surfaces are found to be almost solely dominated by dispersive force contributions, whilst the same with the {011} surfaces are found to have a greater contribution from H-bonding and coulombic forces. The increased surface rugosity, at the molecular level of the {011} surfaces, results in a favourable docking site in a surface 'valley', not present in the {100} and {001} surfaces. The H-bonding solvents ethanol, acetonitrile and ethyl acetate are found to strongly interact with the {011} surfaces and weakly with the {001} surfaces, with the {011} interactions having a much greater contribution from H-bonding and coulombic forces. The interaction energies of the apolar and aprotic solvent toluene, with the {011} and {001} surfaces, are found to be very close. Toluene is found having slightly stronger interactions with the {001} than the {011} surfaces, which are all dominated by dispersive interactions. The ratio of the average energy of the top 100 solvent interactions with the {001} surface divided by the average energy of the top 100 interactions with the {011} surface is compared to the ratio of the experimentally measured growth rates of the same forms. In general, the interaction energy ratio is found to have an inverse ratio with the growth rates, implying that the solvents which are calculated to interact strongly with a particular surface are impeding the growth of that surface and reducing the growth rate, in turn impacting upon the final morphology of the material.

Alternative splicing associated with phenotypic plasticity in the bumble bee Bombus terrestris.

Phenotypic plasticity is when one genome can produce more than one phenotype. The caste system found in many social insects is an important example of plasticity. Several studies have examined gene expression in social insect developmental and caste differences. Changes in gene expression, however, are not the only source of phenotypic plasticity. Here, we investigate the role of alternative splicing in the buff-tailed bumble bee Bombus terrestris. We found that 5,458 genes in B. terrestris (40%) express more than one isoform. Larvae have the lowest level of splicing events, followed by adults and then pupae. We found that when an isoform is expressed in a given caste in the larval stage, it tends to be expressed in all castes at the larval stage. The same is true at the pupal stage. However, we see more complicated interactions between the adult castes with reproductive females showing different isoform expression compared to nonreproductive females and male adults showing the most distinct patterns. We found 455 isoform switching genes, that is genes, where one developmental stage, sex or caste uses a specific isoform and another type uses a different isoform. Among genes displaying isoform switching are some involved in the ecdysteriod pathway, an important system in insect behaviour.

The influence of solution environment on the nucleation kinetics and crystallisability of para-aminobenzoic acid.

The influence of solvent type on the solution thermodynamics, nucleation-kinetics and crystal growth of alpha para-aminobenzoic acid (PABA) crystallising from supersaturated ethanol, acetonitrile and water solutions, is examined using poly-thermal analysis of the metastable zone width. Application of a recently proposed model for analysis of crystallisation kinetics (J. Cryst. Growth, 2010, 312, 698-704) indicates a solvent and concentration dependence of the nucleation mechanism and key nucleation parameters for the alpha form of PABA. The mechanism of nucleation is found to change from instantaneous to progressive with decreasing concentration and also when changing the solvent from ethanol to acetonitrile to water. The dependence of the nucleation mechanism is correlated to the kinetic component of the nucleation rate through calculated values of instantaneously nucleated crystallites, which increase from 1.40 × 109 m-3 in ethanol to 1.08 × 1010 m-3 in acetonitrile to 2.58 × 1010 m-3 in water. This in combination with low calculated number concentrations of interfacial tension between 1.13 and 2.71 mJ m-2, supports the conclusion that the kinetic component of the nucleation rate is more limiting when crystallising PABA from ethanol solutions in comparison to water solutions. This finding is further supported by molecular dynamics simulations of the solvation free energy of PABA, which is found to be greatest in water, -42.4 kJ mol-1 and lowest in ethanol, -58.5 kJ mol-1.

Defining dormancy in mycobacterial disease.

Tuberculosis remains a threat to global health and recent attempts to shorten therapy have not succeeded mainly due to cases of clinical relapse. This has focussed attention on the importance of "dormancy" in tuberculosis. There are a number of different definitions of the term and a similar multiplicity of different in vitro and in vivo models. The danger with this is the implicit assumption of equivalence between the terms and models, which will make even more difficult to unravel this complex conundrum. In this review we summarise the main models and definitions and their impact on susceptibility of Mycobacterium tuberculosis. We also suggest a potential nomenclature for debate. Dormancy researchers agree that factors underpinning this phenomenon are complex and nuanced. If we are to make progress we must agree the terms to be used and be consistent in using them.

Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses: a case for the afferent cholinergic anti-inflammatory pathway?

BACKGROUND: Neuroinflammation in utero may contribute to brain injury resulting in life-long neurological disabilities. The pivotal role of the efferent cholinergic anti-inflammatory pathway (CAP) in controlling inflammation, e.g., by inhibiting the HMGB1 release, via the macrophages' α7 nicotinic acetylcholine receptor (α7nAChR) has been described in adults, but its importance in the fetus is unknown. Moreover, it is unknown whether CAP may also exert anti-inflammatory effects on the brain via the anatomically predominant afferent component of the vagus nerve. METHODS: We measured microglial activation in the ovine fetal brain near term 24 h after the umbilical cord occlusions mimicking human labor versus controls (no occlusions) by quantifying HMGB1 nucleus-to-cytosol translocation in the Iba1+ and α7nAChR+ microglia. Based on multiple clinical studies in adults and our own work in fetal autonomic nervous system, we gauged the degree of CAP activity in vivo using heart rate variability measure RMSSD that reflects fluctuations in vagus nerve activity. RESULTS: RMSSD correlated to corresponding plasma IL-1ß levels at R = 0.57 (p = 0.02, n = 17) and to white matter microglia cell counts at R = -0.89 (p = 0.03). The insult increased the HMGB1 translocation in α7nAChR+ microglia in a brain region-dependent manner (p < 0.001). In parallel, RMSSD at 1 h post insult correlated with cytosolic HMGB1 of thalamic microglia (R = -0.94, p = 0.005), and RMSSD at pH nadir correlated with microglial α7nAChR in the white matter (R = 0.83, p = 0.04). Overall, higher RMSSD values correlated with lower HMGB1 translocation and higher α7nAChR intensity per area in a brain region-specific manner. CONCLUSIONS: Afferent fetal CAP may translate increased vagal cholinergic signaling into suppression of cerebral inflammation in response to near-term hypoxic acidemia as might occur during labor. Our findings suggest a new control mechanism of fetal neuroinflammation via the vagus nerve, providing novel possibilities for its non-invasive monitoring in utero and for targeted treatment.

Alumni-based evaluation of a novel veterinary curriculum: are Nottingham graduates prepared for clinical practice?

INTRODUCTION: Outcomes-based education has been the core of the curriculum strategy of the Nottingham School of Veterinary Medicine and Science (SVMS) since its inception in 2006. As part of the ongoing curriculum evaluation, the first two graduating cohorts were invited to provide an appraisal of their preparation by the SVMS curriculum for their role in clinical practice. This paper provides brief accounts of the SVMS curriculum model, the development of the evaluation instrument and the findings of the alumni survey. MATERIALS AND METHODS: The evaluation instrument contained 25 attributes expected of SVMS graduates. Alumni rated their preparation for practice in relation to each attribute. RESULTS: The four highest rated characteristics were compassion for animals and the application of ethics to animal welfare; communication skills; recognising own limitations and seeking help and advice where needed and clinical examination skills. The four lowest rated were clinical case management and therapeutic strategies; dealing with veterinary public health and zoonotic issues; knowledge of current veterinary legislation and dealing with emergency and critical care cases. Free text responses were in line with these quantitative findings. CONCLUSION: The results indicate that this sample of SVMS graduates were satisfied with their undergraduate education and felt well prepared for their role in clinical practice.

Towards an understanding of the nucleation of alpha-para amino benzoic acid from ethanolic solutions: a multi-scale approach.

The molecular assembly and subsequent nucleation of para-amino benzoic acid (PABA) from ethanolic solutions is probed using a multi-scale and multi-technique approach. This is applied by examining and interrelating information regarding the molecular, solution-state, cluster, solid-state and surface structures to understand why the alpha form of PABA is crystallised in preference to its low temperature beta form. Calculations suggest that conformational changes within the solute molecule play little or no role in directing the nucleation of either the alpha or beta crystal forms. Combined ab initio and molecular dynamics calculations of the stability of small clusters in solution suggests that the hydrogen-bonded carboxylic acid dimers, present in the alpha structure, are the most stable in solution and play a major role in the self-assembly and polymorphic expression of the alpha form in ethanol in preference to the beta form. These calculations are in good agreement with X-ray small-angle scattering analysis which reveals the presence of PABA clusters in ethanol which are consistent with the size and shape of a carboxylic acid dimer. SAXS studies also reveal the presence of larger cluster structures in a size range 10-40 nm which appear to grow, perhaps reflecting a change in the balance between monomers and dimers within the solution during the nucleation process. The results of crystallisation-kinetics experiments indicate an instantaneous nucleation mechanism where the number of instantaneously nucleated crystallites is calculated to be 1360-660 nuclei per ml and the subsequent growth is found to be only rate limited by diffusion of the growth unit to the crystallite surface. A linear dependence of growth rate with respect to supersaturation is observed for the (0 1 -1) capping face, which is associated with strong π-π stacking interactions. This is consistent with a solid-on-solid mechanism associated with surface roughened growth and concomitant poor lattice-perfection. Conversely, the side (1 0 -1) surface has a growth mechanism consistent with a 2D nucleation birth and spread mechanism. Hence, these mechanisms result in very fast growth along the b-axis and the needle-like morphology that is observed for alpha-PABA.

Transition in sexual system and sex chromosome evolution in the tadpole shrimp Triops cancriformis.

Transitions in sexual system and reproductive mode may affect the course of sex chromosome evolution, for instance by altering the strength of sexually antagonistic selection. However, there have been few studies of sex chromosomes in systems where such transitions have been documented. The European tadpole shrimp, Triops cancriformis, has undergone a transition from dioecy to androdioecy (a sexual system where hermaphrodites and males coexist), offering an excellent opportunity to test the impact of this transition on the evolution of sex chromosomes. To identify sex-linked markers, to understand mechanisms of sex determination and to investigate differences between sexual systems, we carried out a genome-wide association study using restriction site-associated DNA sequencing (RAD-seq) of 47 males, females and hermaphrodites from one dioecious and one androdioecious population. We analysed 22.9 Gb of paired-end sequences and identified and scored >3000 high coverage novel genomic RAD markers. Presence-absence of markers, single-nucleotide polymorphism association and read depth identified 52 candidate sex-linked markers. We show that sex is genetically determined in T. cancriformis, with a ZW system conserved across dioecious and androdioecious populations and that hermaphrodites have likely evolved from females. We also show that the structure of the sex chromosomes differs strikingly, with a larger sex-linked region in the dioecious population compared with the androdioecious population.

Role of GPR30 in mediating estradiol effects on acetylcholine release in the hippocampus.

We have hypothesized that estradiol enhances basal forebrain cholinergic function and cognitive performance, at least in part, via activation of the novel estrogen receptor GPR30. Here we evaluated the effects of estradiol, G-1 (a selective GPR30 agonist), and tamoxifen (TAM; an ERα/ERß antagonist that also acts as a GPR30 agonist), on acetylcholine (ACh) release in the hippocampus, as well as the ability to block the effects of 17ß-estradiol (E) or TAM with the GPR30 antagonist G-15. Note that G-1 was included to evaluate the effects of selectively activating GPR30, whereas TAM was included to differentiate effects of E associated with activation of GPR30 vs. ERα or ERß. The study was designed to test effects on potassium-stimulated release, as well as on ACh release stimulated by feeding. Effects of feeding were included because the tasks we used previously to demonstrate beneficial effects of E on cognitive performance were motivated by food reward, and we hypothesized that E may enhance performance by increasing ACh release in association with that reward. Ovariectomized rats were treated for 1week, and ACh release was evaluated using in vivo microdialysis. In addition, rats were fed at the same time daily for several days and were fasted overnight prior to microdialysis. For each rat, ACh release was evaluated under basal conditions, in response to feeding, and in response to elevated potassium. Both feeding and elevated potassium increased ACh release in the hippocampus. In response to feeding, E, G-1, and TAM all significantly increased the percent change in release. The effects of E and TAM were blocked by G-15, and the effects of combining E+TAM did not differ significantly from the effects of E or TAM alone. In response to elevated potassium, E, and TAM significantly increased the percent change in ACh release. G-1 produced a slightly lesser effect. The effect of TAM was reduced by G-15, but the effect of E was not. These findings suggest that activation of GPR30 is both necessary and sufficient to account for the effects of E on ACh release associated with feeding. In contrast, activation of GPR30 appears to be sufficient, but may not be necessary for increased release associated with elevated potassium. The changes associated with feeding are consistent with the effects of E, G-1 and G-15 on acquisition of a spatial learning task previously described. These data confirm and extend previous reports, and support a hypothesis wherein E treatment can improve learning on specific tasks by activating GPR30 and enhancing ACh release in association with food reward.

A simple and inexpensive point-of-care test for hepatitis B surface antigen detection: serological and molecular evaluation.

Early identification of chronic hepatitis B is important for optimal disease management and prevention of transmission. Cost and lack of access to commercial hepatitis B surface antigen (HBsAg) immunoassays can compromise the effectiveness of HBV screening in resource-limited settings and among marginalized populations. High-quality point-of-care (POC) testing may improve HBV diagnosis in these situations. Currently available POC HBsAg assays are often limited in sensitivity. We evaluated the NanoSign(®) HBs POC chromatographic immunoassay for its ability to detect HBsAg of different genotypes and with substitutions in the 'a' determinant. Thirty-seven serum samples from patients with HBV infection, covering HBV genotypes A-G, were assessed for HBsAg titre with the Roche Elecsys HBsAg II quantification assay and with the POC assay. The POC assay reliably detected HBsAg at a concentration of at least 50 IU/mL for all genotypes, and at lower concentrations for some genotypes. Eight samples with substitutions in the HBV 'a' determinant were reliably detected after a 1/100 dilution. The POC strips were used to screen serum samples from 297 individuals at risk for HBV in local clinical settings (health fairs and outreach events) in parallel with commercial laboratory HBsAg testing (Quest Diagnostics EIA). POC testing was 73.7% sensitive and 97.8% specific for detection of HBsAg. Although the POC test demonstrated high sensitivity over a range of genotypes, false negatives were frequent in a clinical setting. Nevertheless, the POC assay offers advantages for testing in both developed and resource-limited countries due to its low cost (0.50$) and immediately available results.

An analysis of sodium, total fat and saturated fat contents of packaged food products advertised in Bronx-based supermarket circulars.

Americans' consumption of sodium, fat, and saturated fat exceed federally recommended limits for these nutrients and has been identified as a preventable leading cause of hypertension and cardiovascular disease. More than 40% of the Bronx population comprises African-Americans, who have increased risk and earlier onset of hypertension and are also genetically predisposed to salt-sensitive hypertension. This study analyzed nutrition information for packaged foods advertised in Bronx-based supermarket circulars. Federally recommended limits for sodium, saturated fat and total fat contents were used to identify foods that were high in these nutrients. The proportion of these products with respect to the total number of packaged foods was calculated. More than a third (35%) and almost a quarter (24%) of the 898 advertised packaged foods were high in saturated fat and sodium respectively. Such foods predominantly included processed meat and fish products, fast foods, meals, entrees and side dishes. Dairy and egg products were the greatest contributors of high saturated fat. Pork and beef products, fast foods, meals, entrees and side dishes had the highest median values for sodium, total fat and saturated fat content. The high proportion of packaged foods that are high in sodium and/or saturated fat promoted through supermarket circulars highlights the need for nutrition education among consumers as well as collaborative public health measures by the food industry, community and government agencies to reduce the amounts of sodium and saturated fat in these products and limit the promotion of foods that are high in these nutrients.

Cardiac output is not a significant source of low frequency mean arterial pressure variability.

Spontaneous mean arterial pressure (MAP) variability may be mainly due to fluctuations in cardiac output (CO) and total peripheral resistance (TPR). While high frequency (HF ∼ 0.25 Hz) oscillations in MAP are ultimately driven by respiration, the source of low frequency (LF ∼ 0.1 Hz) fluctuations has not been fully elucidated. It is known that CO buffers these oscillations, but there is no evidence on its potential role in also generating them. The main goal was to determine whether CO is a source of LF variability in MAP. Six dogs were chronically instrumented to obtain beat-to-beat measurements of CO and MAP while the dogs were fully awake and at rest. A causal dynamic model was identified to relate the fluctuations in CO to MAP. The model was then used to predict the MAP fluctuations from the CO fluctuations. The CO fluctuations were able to predict about 70% of the MAP oscillations in the HF band but showed no predictive value in the LF band. Hence, respiration induces CO fluctuations in the HF band that, in turn, cause MAP oscillations, while TPR fluctuations appear to be the dominant mediator of LF fluctuations of MAP. CO is not a significant source of these oscillations, and it may only be responsible for dampening them, likely through the baroreflex.

Chronic treatment with a GPR30 antagonist impairs acquisition of a spatial learning task in young female rats.

We hypothesize that the beneficial effects of estradiol on cognitive performance may be mediated through GPR30, a putative membrane target of estrogens. Recently we showed that administration of a selective GPR30 agonist (G-1) to ovariectomized rats enhanced acquisition of a delayed matching-to-position (DMP) T-maze task and increased potassium-stimulated acetylcholine release in the hippocampus, similar to estradiol (E2) (Hammond et al., 2009). The present study tested whether treating with a selective GPR30 antagonist (G-15) would impair spatial learning in gonadally intact rats and in ovariectomized (OVX) rats treated with E2. As predicted, G-15 dose-dependently impaired DMP acquisition both in gonadally intact rats and in OVX rats treated with E2. G-15 specifically reduced the rate of acquisition, and this effect was associated with an increased predisposition to adopt a persistent turn. In contrast, G-15 alone at the highest dose had no significant effect on DMP acquisition in OVX controls. The effects were task dependent, as similar effects of G-15 were not observed in gonadally intact rats tested on an operant discrimination/reversal learning task motivated by the same food reward. This suggests that the effects on DMP acquisition were not due to effects on motivation for food. Effects of G-15 on DMP acquisition were similar to previously published work showing significant impairment produced by selective cholinergic denervation of the hippocampus. These data suggest that GPR30 can play an important role in mediating the effects of estradiol on spatial learning, possibly by mediating estradiol effects on basal forebrain cholinergic function.

Enhancing clinical learning in the workplace: a qualitative study.

Workplace learning (WPL) is seen as an essential component of clinical veterinary education by the veterinary profession. This study sought to understand this type of learning experience more deeply. This was done utilising observations of students on intramural rotations (IMR) and interviews with students and clinical staff. WPL was seen as an opportunity for students to apply knowledge and develop clinical and professional skills in what is generally regarded as a safe, authentic environment. Clinical staff had clear ideas of what they expected from students in terms of interest, engagement, professionalism, and active participation, where this was appropriate. In contrast, students often did not know what to expect and sometimes felt under-prepared when entering the workplace, particularly in a new species area. With the support of staff acting as mentors, students learned to identify gaps in their knowledge and skills, which could then be addressed during specific IMR work placements. Findings such as these illustrate both the complexities of WPL and the diversity of different workplace settings encountered by the students.