Optimising the hygiene of a liquid feeding system to improve the quality of liquid feed for pigs.

Poor feeding system hygiene may contribute to uncontrolled spontaneous fermentation in liquid pig feed and its associated undesirable effects. This study aimed to determine the effects of an intensive sanitisation programme in a grow-finisher liquid feeding system by monitoring microbiological and physico-chemical parameters of liquid feed and microbial colonisation of the feeding system surfaces. The sanitisation programme involved a combination of physical and chemical cleaning between batches of grow-finisher pigs, combined with nightly rinsing of the system with an organic acid blend. Improved hygiene of the internal surfaces of the mixing tank and feed pipeline, particularly until week 5 post-cleaning, was evidenced by reduced counts of lactic acid bacteria, total aerobes, Enterobacteriaceae, yeasts and moulds and decreased adenosine triphosphate concentrations. Enterobacteriaceae and moulds remained undetectable on pipeline surfaces for 10 weeks. Scanning electron microscopy of the feed pipelines confirmed these findings. Conversely, the impact on liquid feed microbiology was minimal and short-lived. However, acetic acid, ethanol and biogenic amine concentrations decreased in the feed post-cleaning and no gross energy losses were observed. Therefore, by controlling surface microbial communities on liquid feeding systems via implementation of the sanitisation programme developed in the current study, on-farm liquid feed quality should be improved.

A deep convolutional neural network ensemble for composite identification of pulmonary nodules and incidental findings on routine PET/CT.

AIM: To evaluate primary and secondary pathologies of interest using an artificial intelligence (AI) platform, AI-Rad Companion, on low-dose computed tomography (CT) series from integrated positron-emission tomography (PET)/CT to detect CT findings that might be overlooked. MATERIALS AND METHODS: One hundred and eighty-nine sequential patients who had undergone PET/CT were included. Images were evaluated using an ensemble of convolutional neural networks (AI-Rad Companion, Siemens Healthineers, Erlangen, Germany). The primary outcome was detection of pulmonary nodules for which the accuracy, identity, and intra-rater reliability was calculated. For secondary outcomes (binary detection of coronary artery calcium, aortic ectasia, vertebral height loss), accuracy and diagnostic performance were calculated. RESULTS: The overall per-nodule accuracy for detection of lung nodules was 0.847. The overall sensitivity and specificity for detection of lung nodules was 0.915 and 0.781. The overall per-patient accuracy for AI detection of coronary artery calcium, aortic ectasia, and vertebral height loss was 0.979, 0.966, and 0.840, respectively. The sensitivity and specificity for coronary artery calcium was 0.989 and 0.969. The sensitivity and specificity for aortic ectasia was 0.806 and 1. CONCLUSION: The neural network ensemble accurately assessed the number of pulmonary nodules and presence of coronary artery calcium and aortic ectasia on low-dose CT series of PET/CT. The neural network was highly specific for the diagnosis of vertebral height loss, but not sensitive. The use of the AI ensemble can help radiologists and nuclear medicine physicians to catch CT findings that might be overlooked.

A comparison of physical performance during one- and two-person simulated casualty drags.

The ability to drag a casualty to safety is critical for numerous physically demanding occupations. This study aimed to establish whether the pulling forces during a one-person 55 kg simulated casualty drag is representative of a two-person 110 kg drag. Twenty men completed up to 12 × 20m simulated casualty drags using a drag bag (55/110 kg) on a grassed sports pitch, with completion times and forces exerted measured. Completion time for the one-person 55 and 110 kg drags were 9.56 ± 1.18s and 27.08 ± 7.71s. Completion time for the 110 kg two-person drags for forwards and backwards iterations were 8.36 ± 1.23s and 11.04 ± 1.11s. The average individual force exerted during the one-person 55 kg drag was equivalent to the average individual contribution during the two-person 110 kg drag (t(16) = 3.3780, p < 0.001); suggesting a one-person 55 kg simulated casualty drag is representative of the individual contribution to a two-person 110 kg simulated casualty drag. Individual contributions can however vary during two-person simulated casualty drags.

Validation of a suite of ERP and QEEG biomarkers in a pre-competitive, industry-led study in subjects with schizophrenia and healthy volunteers.

OBJECTIVE: Complexity and lack of standardization have mostly limited the use of event-related potentials (ERPs) and quantitative EEG (QEEG) biomarkers in drug development to small early phase trials. We present results from a clinical study on healthy volunteers (HV) and patients with schizophrenia (SZ) that assessed test-retest, group differences, variance, and correlation with functional assessments for ERP and QEEG measures collected at clinical and commercial trial sites with standardized instrumentation and methods, and analyzed through an automated data analysis pipeline. METHODS: 81 HV and 80 SZ were tested at one of four study sites. Subjects were administered two ERP/EEG testing sessions on separate visits. Sessions included a mismatch negativity paradigm, a 40 Hz auditory steady-state response paradigm, an eyes-closed resting state EEG, and an active auditory oddball paradigm. SZ subjects were also tested on the Brief Assessment of Cognition (BAC), Positive and Negative Syndrome Scale (PANSS), and Virtual Reality Functional Capacity Assessment Tool (VRFCAT). RESULTS: Standardized ERP/EEG instrumentation and methods ensured few test failures. The automated data analysis pipeline allowed for near real-time analysis with no human intervention. Test-retest reliability was fair-to-excellent for most of the outcome measures. SZ subjects showed significant deficits in ERP and QEEG measures consistent with published academic literature. A subset of ERP and QEEG measures correlated with functional assessments administered to the SZ subjects. CONCLUSIONS: With standardized instrumentation and methods, complex ERP/EEG testing sessions can be reliably performed at clinical and commercial trial sites to produce high-quality data in near real-time.

Changes in physical performance during British Army Junior Entry, British Army Standard Entry and Royal Air Force Basic Training.

INTRODUCTION: The purpose was to quantify physical performance in men and women during British Army Junior Entry (Army-JE), British Army Standard Entry (Army-SE) and Royal Air Force (RAF) basic training (BT). DESIGN: Prospective longitudinal study. METHODS: 381 participants ((339 men and 42 women) n=141 Army-JE, n=132 Army-SE, n=108 RAF) completed a 2 km run, medicine ball throw (MBT) and isometric mid-thigh pull (MTP), pre-BT and post-BT. To examine changes in pre-BT to post-BT physical test performance, for each course, paired Student t-test and Wilcoxon test were applied to normally and non-normally distributed data, respectively, with effect sizes reported as Cohen's D and with rank biserial correlations, respectively. A one-way between-subjects analysis of variance (ANOVA) (or Welch ANOVA for non-normally distributed data) compared performance between quartiles based on test performance pre-BT. Where the main tests statistic, p value and effect sizes identified likely effect of quartile, post hoc comparisons were made using Games-Howell tests with Tukey's p value. Data are presented as mean±SD, with statistical significance set at p<0.05. RESULTS: During BT, 2 km run time improved by 13±46 s (-2.1%±8.1%), 30±64 s (-4.8%±12.3%) and 24±27 s (-4.5%±5.1%) for Army-JE, Army-SE and RAF, respectively (all p<0.005). MBT distance increased by 0.27±0.28 m (6.8%±7.0%) for Army-JE (p<0.001) and 0.07±0.46 m (2.3%±10.9%) for Army-SE (p=0.040), but decreased by 0.08±0.27 m (-1.4%±6.0%) for RAF (p=0.002). MTP force increased by 80±281 n (10.8%±27.6%) for Army-JE (p<0.001) and did not change for Army-SE (-36±295 n, -0.7%±20.6%, p=0.144) or RAF (-9±208 n, 1.0±17.0, p=0.603). For all tests and cohorts, participants in the lowest quartile of pre-BT performance scores demonstrated greater improvements, compared with participants in the highest quartile (except Army-JE MBT, ∆% change similar between all quartiles). CONCLUSIONS: Changes in physical performance were observed for the three fitness tests following the different BT courses, and recruits with the lowest strength and aerobic fitness experienced greatest improvements.

Employing the theory of planned behaviour to design an e-cigarette education resource for use in secondary schools.

BACKGROUND: An extended version of the theory of planned behaviour (TPB) was used to inform the design of a framework for an educational resource around e-cigarette use in young people. METHODS: A sequential exploratory design was employed. In Phase 1, elicited behavioural, normative and control beliefs, via 7 focus groups with 51 participants, aged 11-16 years, identified salient beliefs around e-cigarette use. These were used to construct a questionnaire administered to 1511 young people aged 11-16 years, which determined predictors of e-cigarette use and ever use. In Phase 2, sociodemographic variables, e-cigarette knowledge, access, use, marketing and purchasing of e-cigarettes and smoking behaviour were also gathered. The composite findings from Phase 1 and 2 informed the design of a post primary educational resource in Phase 3 around e-cigarette use. RESULTS: Current e-cigarette use was 4%, with almost 23% reporting ever use, suggesting current use is stable but experimentation may be increasing in this cohort. Sociodemographic variables, knowledge of e-cigarettes, smoking behaviour and TPB variables (direct and indirect measures of attitudes, subjective norm, and perceived behavioural control) accounted for 17% of the variance in current e-cigarette use, with higher intentions to use e-cigarettes within the next month, having the strongest impact on use (p < 0.001), followed by self-efficacy (p = 0.016). Sociodemographic and TPB variables accounted for 65% of the variance in intentions to use e-cigarettes in the next month; current e-cigarette use (p < 0.001), more positive attitudes (p < 0.001), stronger social influence (p < 0.001), higher self-efficacy (p < 0.001), higher control beliefs (p < 0.001) and greater motivation to use e-cigarettes (p < 0.001) were the main predictors of intentions. Phases 1 and 2 informed the mapping of key predictors of intentions and use of e-cigarettes onto the Theoretical Domains Framework, which identified appropriate intervention functions and behaviour change techniques. CONCLUSIONS: This paper is the first to bridge the theoretical-practice gap in an area of significant public health importance through the development of a framework for a novel theory driven school-based educational resource aimed at reducing experimentation and uptake of e-cigarette use in young people.

MOP and NOP receptor interaction: Studies with a dual expression system and bivalent peptide ligands.

Opioids targeting mu;µ (MOP) receptors produce analgesia in the peri-operative period and palliative care. They also produce side effects including respiratory depression, tolerance/dependence and addiction. The N/OFQ opioid receptor (NOP) also produces analgesia but is devoid of the major MOP side effects. Evidence exists for MOP-NOP interaction and mixed MOP-NOP ligands produce analgesia with reduced side effects. We have generated a HEKMOP/NOP human expression system and used bivalent MOP-NOP and fluorescent ligands to (i) probe for receptor interaction and (ii) consequences of that interaction. We used HEKMOP/NOP cells and two bivalent ligands; Dermorphin-N/OFQ (MOP agonist-NOP agonist; DeNO) and Dermorphin-UFP101 (MOP agonist-NOP antagonist; De101). We have determined receptor binding profiles, GTPγ[35S] binding, cAMP formation and ERK1/2 activation. We have also probed MOP and NOP receptor interactions in HEK cells and hippocampal neurones using the novel MOP fluorescent ligand, DermorphinATTO488 and the NOP fluorescent ligand N/OFQATTO594. In HEKMOP/NOP MOP ligands displaced NOP binding and NOP ligands displaced MOP binding. Using fluorescent probes in HEKMOP/NOP cells we demonstrated MOP-NOP probe overlap and a FRET signal indicating co-localisation. MOP-NOP were also co-localised in hippocampal tissue. In GTPγ[35S] and cAMP assays NOP stimulation shifted the response to MOP rightwards. At ERK1/2 the response to bivalent ligands generally peaked later. We provide evidence for MOP-NOP interaction in recombinant and native tissue. NOP activation reduces responsiveness of MOP activation; this was shown with conventional and bivalent ligands.

Effects of dietary supplementation with a laminarin-rich extract on the growth performance and gastrointestinal health in broilers.

Restriction in antimicrobial use in broiler chicken production is driving the exploration of alternative feed additives that will support growth through the promotion of gastrointestinal health and development. The objective of this study was to determine the effects of dietary inclusion of laminarin on growth performance, the expression of nutrient transporters, markers of inflammation and intestinal integrity in the small intestine and composition of the caecal microbiota in broiler chickens. Two-hundred-and-forty day-old male Ross 308 broiler chicks (40.64 (3.43 SD) g) were randomly assigned to: (T1) basal diet (control); (T2) basal diet + 150 ppm laminarin; (T3) basal diet + 300 ppm laminarin (5 bird/pen; 16 pens/treatment). The basal diet was supplemented with a laminarin-rich Laminaria spp. extract (65% laminarin) to achieve the two laminarin inclusion levels (150 and 300 ppm). Chick weights and feed intake was recorded weekly. After 35 days of supplementation, one bird per pen from the control and best performing (300 ppm) laminarin groups were euthanized. Duodenal, jejunal and ileal tissues were collected for gene expression analysis. Caecal digesta was collected for microbiota analysis (high-throughput sequencing and QPCR). Dietary supplementation with 300 ppm laminarin increased both final body weight (2033 vs. 1906 ± 30.4, P < 0.05) and average daily gain (62.3 vs. 58.2 ± 0.95, P < 0.05) compared to the control group and average daily feed intake (114.1 vs. 106.0 and 104.5 ± 1.77, P < 0.05) compared to all other groups. Laminarin supplementation at 300 ppm increased the relative and absolute abundance of Bifidobacterium (P < 0.05) in the caecum. Laminarin supplementation increased the expression of interleukin 17A (IL17A) in the duodenum, claudin 1 (CLDN1) and toll-like receptor 2 (TLR2) in the jejunum and IL17A, CLDN1 and SLC15A1/peptide transporter 1 (SLC15A1/PepT1) in the ileum (P < 0.05). In conclusion, supplementation with laminarin is a promising dietary strategy to enhance growth performance and 300 ppm was the optimal inclusion level with which to promote a beneficial profile of the gastrointestinal microbiota in broiler chickens.

Microbiological assessment of liquid feed for finisher pigs on commercial pig units.

AIMS: To investigate the microbiological and nutritional quality of liquid finisher pig feed on commercial production units and the factors influencing this. METHODS AND RESULTS: Microbiological and physio-chemical analyses were performed on liquid feed sampled from the mixing tank and troughs of the finisher section of eight commercial pig units. Lactic acid bacteria, yeast and Escherichia coli counts, as well as lactic acid, ethanol and acetate concentrations were higher in residual feed sampled from the troughs compared with mixing tank samples (P < 0·001). Feed pH, as well as lysine, methionine and threonine concentrations and gross energy were all lower in the residual trough samples (P < 0·001). Liquid co-products reduced E. coli counts in the residual trough samples (P < 0·05), pH in the mixing tank (P < 0·01) and fresh trough samples (P < 0·05) and mould counts at all three sampling locations (P < 0·01) but sanitation practices had no impact. CONCLUSIONS: Even when considered unfermented, a considerable degree of spontaneous fermentation occurs in liquid feed, with resultant negative effects on nutritional quality. SIGNIFICANCE AND IMPACT OF THE STUDY: This is one of the first studies showing that uncontrolled fermentation of fresh liquid pig feed is commonplace on commercial units, highlighting the need for implementation of suitable control strategies.

Colonic microbiome profiles for improved feed efficiency can be identified despite major effects of farm of origin and contemporary group in pigs.

While feed efficiency (FE) is a trait of great economic importance to the pig industry, the influence of the intestinal microbiome in determining FE is not well understood. The objective of this experiment was to determine the relative influence of FE and farm of birth on the pig colonic microbiome. Animals divergent in residual feed intake (RFI) were sourced from two geographically distinct locations (farms A + B) in Ireland. The 8 most efficient (low RFI (LRFI)) and 8 least efficient (high RFI, (HRFI)) pigs from farm A and 12 LRFI and 12 HRFI pigs from farm B were sacrificed. Colonic digesta was collected for microbial analysis using 16S ribosomal RNA gene sequencing and also for volatile fatty acid analysis. The α-diversity differed between the farms in this study, with pigs from farm A having greater diversity based on Shannon and InvSimpson measures compared to pigs from farm B (P < 0.05), with no difference identified in either Chao1 or observed measures of diversity (P > 0.05). In the analysis of ß-diversity, pigs clustered based on farm of birth rather than RFI. Variation in the management of piglets, weight of the piglets, season of the year, sanitary status and dam dietary influence could potentially be causative factors in this large variation between farms. However, despite significant variation in the microbial profile between farms, consistent taxonomic differences were identified between RFI groups. Within the phylum Bacteroidetes, the LRFI pigs had increased abundance of BS11 (P < 0.05) and a tendency toward increased Bacteroidaceae (P < 0.10) relative to the HRFI group. At genus level, the LRFI pigs had increased abundance of Colinsella (P < 0.05), a tendency toward increased Bacteroides and CF231 (P < 0.10). At species level, Ruminococcus flavefaciens had increased abundance in the LRFI compared to the HRFI animals. In conclusion, while farm of birth has a substantial influence on microbial diversity in the pig colon, a microbial signature indicative of FE status was apparent.

Effect of dietary L-carnitine supplementation to sows during gestation and/or lactation on sow productivity, muscle maturation and lifetime growth in progeny from large litters.

Genetic selection for increased sow prolificacy has resulted in decreased mean piglet birth-weight. This study aimed to investigate the effect of L-carnitine (CAR) supplementation to sows during gestation and/or lactation on sow productivity, semitendinosus muscle (STM) maturity, and lifetime growth in progeny. Sixty-four sows were randomly assigned to one of four dietary treatments at breeding until weaning; CONTROL (0mg CAR/d), GEST (125mg CAR/d during gestation), LACT (250mg CAR/d during lactation), and BOTH (125mg CAR/d during gestation & 250mg CAR/d during lactation). The total number of piglets born per litter was greater for sows supplemented with CAR during gestation (17.3 v 15.8 ± 0.52; P<0.05). Piglet birth-weight (total and live) was unaffected by sow treatment (P>0.05). Total myofibre number (P=0.08) and the expression level of selected myosin heavy chain genes in the STM (P<0.05) was greater in piglets of sows supplemented with CAR during gestation. Pigs from sows supplemented with CAR during gestation had lighter carcasses at slaughter than pigs from non-supplemented sows during gestation (83.8 v 86.7 ± 0.86kg; P<0.05). In conclusion, CAR supplementation during gestation increased litter size at birth without compromising piglet birth-weight. Results also showed that the STM of piglets born to sows supplemented with CAR during gestation was more developed at birth. However, carcass weight at slaughter was reduced in progeny of sows supplemented with CAR during gestation. The CAR supplementation strategy applied during gestation in this study could be utilized by commercial pork producers to increase sow litter size and improve offspring muscle development.

Laminarin-rich extract improves growth performance, small intestinal morphology, gene expression of nutrient transporters and the large intestinal microbial composition of piglets during the critical post-weaning period.

The identification of natural bioactive compounds which can prevent the post-weaning growth check and enhance gastrointestinal health in the absence of in-feed medications is an urgent priority for the swine industry. The objective of this experiment was to determine the effects of increasing dietary inclusion levels of laminarin in the first 14 d post-weaning on pig growth performance and weaning associated intestinal dysfunction. At weaning, ninety-six pigs (8·4 (sd 1·09) kg) (meatline boars × (large white × landrace sows)) were blocked by live weight, litter and sex and randomly assigned to: (1) basal diet; (2) basal + 100 parts per million (ppm) laminarin; (3) basal + 200 ppm laminarin and (4) basal + 300 ppm laminarin (three pigs/pen). The appropriate quantity of a laminarin-rich extract (65 % laminarin) was added to the basal diet to achieve the above dietary inclusion levels of laminarin. After 14 d of supplementation, eight pigs from the basal group and the best-performing laminarin group were euthanised for sample collection. The 300 ppm laminarin group was selected as this group had higher ADFI compared with all other groups and higher ADG than the basal group (P < 0·05). Laminarin supplementation increased villus height in the duodenum and jejunum (P < 0·05). Laminarin supplementation increased the expression of SLC2A8/GLUT8 in the duodenum, SLC2A2/GLUT2, SLC2A7/GLUT7, SLC15A1/PEPT1 and FABP2 in the jejunum and SLC16A1/MCT1 in the colon. Laminarin supplementation reduced Enterobacteriaceae numbers in the caecum (P < 0·05) and increased lactobacilli numbers (P < 0·05), total volatile fatty acid concentrations and the molar proportions of butyrate (P < 0·01) in the colon. In conclusion, 300 ppm laminarin from a laminarin-rich extract has potential, as a dietary supplement, to improve performance and prevent post-weaning intestinal dysfunction.

Use of aspirin, other nonsteroidal anti-inflammatory drugs and acetaminophen and risk of endometrial cancer: the Epidemiology of Endometrial Cancer Consortium.

BACKGROUND: Regular use of aspirin has been associated with a reduced risk of cancer at several sites but the data for endometrial cancer are conflicting. Evidence regarding use of other analgesics is limited. PATIENTS AND METHODS: We pooled individual-level data from seven cohort and five case-control studies participating in the Epidemiology of Endometrial Cancer Consortium including 7120 women with endometrial cancer and 16 069 controls. For overall analyses, study-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression and combined using random-effects meta-analysis; for stratified analyses, we used mixed-effects logistic regression with study as a random effect. RESULTS: At least weekly use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an approximately 15% reduced risk of endometrial cancer among both overweight and obese women (OR = 0.86 [95% CI 0.76-0.98] and 0.86 [95% CI 0.76-0.97], respectively, for aspirin; 0.87 [95% CI 0.76-1.00] and 0.84 [0.74-0.96], respectively, for non-aspirin NSAIDs). There was no association among women of normal weight (body mass index < 25 kg/m2, Pheterogeneity = 0.04 for aspirin, Pheterogeneity = 0.003 for NSAIDs). Among overweight and obese women, the inverse association with aspirin was stronger for use 2-6 times/week (OR = 0.81, 95% CI 0.68-0.96) than for daily use (0.91, 0.80-1.03), possibly because a high proportion of daily users use low-dose formulations. There was no clear association with use of acetaminophen. CONCLUSION: Our pooled analysis provides further evidence that use of standard-dose aspirin or other NSAIDs may reduce risk of endometrial cancer among overweight and obese women.

Novel Temperature-Dependent Development Rate Models for Postdiapause Egg Eclosion of Three Important Arthropod Pests Found in Commercial Christmas Tree Plantations of Southern Québec, Canada.

The balsam twig aphid Mindarus abietinus Koch (Hemiptera: Aphididae), the spruce spider mite Oligonychus ununguis (Jacobi) (Acari: Tetranychidae), and the pine needle scale Chionaspis pinifoliae (Fitch) (Hemiptera: Diaspididae) are three important pests for the Christmas tree industry of Québec, Canada. Temperature-dependent development rates for postdiapause overwintering eggs of these species have never been studied for populations of southern Québec, where the vast majority of Christmas trees are grown. The accumulation of physiological time in growing degree days (GDD) is a standard tool to predict egg eclosion dates for pests, when first generation immatures are most vulnerable to insecticidal control. Development rates for postdiapause eggs were tested at four or five constant temperatures in the 11-23°C range under controlled conditions, based on time before hatching for eggs collected in a balsam fir plantation in late winter. The standard linear model and three published nonlinear models were fitted to the data and compared for their ability to estimate key biological temperature parameters and to predict development rates of postdiapause eggs. Validation of model predictions of egg eclosion time on balsam fir in the field was reasonably accurate using the classical linear model where field-accumulated GDD were calculated with a particular interpretation of the average method based on daily maximum and minimum temperatures. The linear model could predict mean egg eclosion within around 5 d of eclosion dates observed in the field.

Management of Bone Fragility in Primary Care in Ireland.

This study evaluated the prevention of bone fragility fractures in a representative sample of four Irish general practices. The clinical records of 243 patients potentially at risk of bone fragility were studied. One hundred and fourteen (47%) had a dual energy x-ray absorptiometry (DEXA) scan. Osteoporosis was established in 42 (17%) and osteopaenia in 28 (11%). One hundred and fifty-two (63%) were currently being prescribed bisphosphonates. Thirty-four (22%) of those on bisphosphonates did not have a baseline DEXA scan performed prior to commencing treatment and further analysis did not show a clear rationale for initiation of the treatment in this group of patients. Forty-six (30%) patients on bisphosphonates had been prescribed them for over 5 years without any apparent review to see if they were still indicated. There was no record of any of the practices having carried out a fracture risk score assessment prior to commencing bone fragility treatment. The implications are that bone fragility management warrants urgent review.

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.

Genomic and Imaging Biomarkers in Schizophrenia.

Recent large-scale genomic studies have confirmed that schizophrenia is a polygenic syndrome and have implicated a number of biological pathways in its aetiology. Both common variants individually of small effect and rarer but more penetrant genetic variants have been shown to play a role in the pathogenesis of the disorder. No simple Mendelian forms of the condition have been identified, but progress has been made in stratifying risk on the basis of the polygenic burden of common variants individually of small effect, and the contribution of rarer variants of larger effect such as Copy Number Variants (CNVs). Pathway analysis of risk-associated variants has begun to identify specific biological processes implicated in risk for the disorder, including elements of the glutamatergic NMDA receptor complex and post synaptic density, voltage-gated calcium channels, targets of the Fragile X Mental Retardation Protein (FMRP targets) and immune pathways. Genetic studies have also been used to drive genomic imaging approaches to the investigation of brain markers associated with risk for the disorder. Genomic imaging approaches have been applied both to investigate the effect of polygenic risk and to study the impact of individual higher-penetrance variants such as CNVs. Both genomic and genomic imaging approaches offer potential for the stratification of patients and at-risk groups and the development of better biomarkers of risk and treatment response; however, further research is needed to integrate this work and realise the full potential of these approaches.

The variation in chemical composition of barley feed with or without enzyme supplementation influences nutrient digestibility and subsequently affects performance in piglets.

This study investigates the effect of dietary supplementation of a ß-glucanase and ß-xylanase enzyme mix to barley based diets, at two different chemical compositions achieved through different agronomical conditions on growth performance, coefficient of apparent total tract digestibility (CATTD) of nutrients, selected faecal microbial populations and faecal scores in piglets. Sixty-four piglets (11.7 kg (SD 0.96)) housed in pens of two were assigned to one of four dietary treatments (n = 8). The dietary treatments were as follows: (T1) low quality barley diet, (T2) low quality barley diet containing a ß-glucanase and ß-xylanase enzyme supplement, (T3) high quality barley diet and (T4) high quality barley diet containing a ß-glucanase and ß-xylanase enzyme supplement. Piglets offered the low quality barley-based diet had a higher (p < .05) average daily gain (ADG) (0.73 vs. 0.69 kg, SEM 0.001), gain:feed (G:F) ratio (0.61 vs. 0.58 kg, SEM 0.011) and a higher CATTD (p < .001) of dry matter (DM), organic matter (OM), nitrogen (N), ash, gross energy (GE) and neutral detergent fibre (NDF) compared with piglets offered the high quality barley diet. Piglets offered the high quality barley-based diet had reduced faecal scores compared to piglets offered the low quality barley-based diet (2.44 vs. 2.57, SEM 0.036) (p < .05). There was a higher population of Lactobacillus spp. (11.6 vs. 10.5 log gene copy number/g faeces, SEM 0.177) (p < .001) and total volatile fatty acid (VFA) concentration (185 vs. 165 mmol/g faeces, SEM 5.658) (p < .001) in the faeces of piglets offered the high quality barley-based diet compared to piglets offered the low quality barley-based diet. The inclusion of a ß-glucanase and ß-xylanase enzyme complex had no effect on any variable measured. In conclusion, the higher quality barley-based diet showed beneficial effects on the faecal Lactobacillus spp. population and faecal scores of the piglets; however, the higher level of ß-glucans in the diet decreased nutrient digestibility and subsequently decreased the performance.