Comparison of the Efficacy of two Anticonvulsants, Phenytoin and Valproate to Improve PCP and d-amphetamine Induced Deficits in a Reversal Learning Task in the Rat

Recent studies in our laboratory have shown that PCP (phencyclidine) and d-amphetamine induce a cognitive deficit in rats, in a paradigm of potential relevance for the pathology of schizophrenia. Atypical, but not classical antipsychotics and the anticonvulsant, lamotrigine have been shown to prevent a selective reversal learning deficit induced by PCP. In contrast, only haloperidol reversed the d-amphetamine-induced deficit. The present study aimed to explore the ability of two anticonvulsants with differing mechanism of action, valproate and phenytoin to attenuate the cognitive deficits induced by PCP and d-amphetamine in the reversal learning paradigm. PCP at 1.5 mg/kg and d-amphetamine at 0.5 mg/kg both produced a selective and significant reduction in performance of the reversal phase with no effect on the initial phase of the task in female-hooded Lister rats. Valproate (25–200 mg/kg) and phenytoin (25–50 mg/kg) had no effect on performance when administered alone. Valproate (100–200 mg/kg), whose principle action is thought to be the enhancement of GABA transmission, was unable to prevent the cognitive deficit induced by either PCP or d-amphetamine. Conversely, phenytoin (50 mg/kg), a use-dependent sodium channel inhibitor, significantly prevented the deficit induced by PCP, but not d-amphetamine. These results add to our earlier work with lamotrigine, and suggest that sodium channel blockade may be a mechanism by which some anticonvulsant drugs can prevent the PCP-induced deficit. These data have implications for the use of anticonvulsant drugs in the treatment of cognitive or psychotic disorders

Tick parasitism classification from noisy medical records

Much of the health information in the medical domain comes in the form of clinical narratives. The rich semantic information contained in these notes can be modeled to make inferences that assist the decision making process for medical practitioners, which is particularly important under time and resource constraints. However, the creation of such assistive tools is made difficult given the ubiquity of misspellings, unsegmented words and morphologically complex or rare medical terms. This reduces the coverage of vocabulary terms present in commonly used pretrained distributed word representations that are passed as input to parametric models that makes such predictions. This paper presents an ensemble architecture that combines indomain and general word embeddings to overcome these challenges, showing best performance on a binary classification task when compared to various other baselines. We demonstrate our approach in the context of the veterinary domain for the task of identifying tick parasitism from small animals. The best model shows 84.29% test accuracy, showing some improvement over models, which only use pretrained embeddings that are not specifically trained for the medical sub-domain of interest

A systematic review of the organizational, environmental, professional and child and family factors influencing the timing of admission to hospital for children with serious infectious illness

Abstract Background Infection, particularly in the first 5 years of life, is a major cause of childhood deaths globally, many deaths from infections such as pneumonia and meningococcal disease are avoidable, if treated in time. Some factors that contribute to morbidity and mortality can be modified. These include organisational and environmental factors as well as those related to the child, family or professional. Objective Examine what organizational and environmental factors and individual child, family and professional factors affect timing of admission to hospital for children with a serious infectious illness. Design Systematic review. Data sources Key search terms were identified and used to search CINAHL Plus, Medline, ASSIA, Web of Science, The Cochrane Library, Joanna Briggs Institute Database of Systematic Review. Study appraisal methods Primary research (e.g. quantitative, qualitative and mixed methods studies) and literature reviews (e.g., systematic, scoping and narrative) were included if participants included or were restricted to children under 5 years of age with serious infectious illnesses, included parents and/or first contact health care professionals in primary care, urgent and emergency care and where the research had been conducted in OECD high income countries. The Mixed Methods Appraisal Tool was used to review the methodological quality of the studies. Main findings Thirty-six papers were selected for full text review; 12 studies fitted the inclusion criteria. Factors influencing the timing of admission to hospital included the variability in children’s illness trajectories and pathways to hospital, parental recognition of symptoms and clinicians non-recognition of illness severity, parental help-seeking behaviour and clinician responses, access to services, use and non-use of ‘gut feeling’ by clinicians, and sub-optimal management within primary, secondary and tertiary services. Conclusions The pathways taken by children with a serious infectious illness to hospital are complex and influenced by a variety of potentially modifiable individual, organisational, environmental and contextual factors. Supportive, accessible, respectful services that provide continuity, clear communication, advice and safety-netting are important as is improved training for clinicians and a mandate to attend to ‘gut feeling’. Implications Relatively simple interventions such as improved communication have the potential to improve the quality of care and reduce morbidity and mortality in children with a serious infectious illness

PNU-120596, a positive allosteric modulator of α7 nicotinic acetylcholine receptors, reverses a sub-chronic phencyclidineinduced cognitive deficit in the attentional set-shifting task in female rats

yThe α7 nicotinic acetylcholine receptors (nAChRs) have been highlighted as a target for cognitive enhancement in schizophrenia. Adult female hooded Lister rats received sub-chronic phencyclidine (PCP) (2mg/kg) or vehicle i.p. twice daily for 7 days, followed by 7 days’ washout. PCP-treated rats then received PNU-120596 (10mg/kg; s.c.) or saline and were tested in the attentional set-shifting task. Sub-chronic PCP produced a significant cognitive deficit in the extra-dimensional shift (EDS) phase of the task (p < 0.001, compared with vehicle). PNU-120596 significantly improved performance of PCP-treated rats in the EDS phase of the attentional set-shifting task (p < 0.001). In conclusion, these data demonstrate that PNU-120596 improves cognitive dysfunction in our animal model of cognitive dysfunction in schizophrenia, most likely via modulation of α7 nACh receptors.This work was partially funded by Johnson & Johnson Pharmaceutical Research and Development

Herschel observations of EXtraordinary Sources: Analysis of the full Herschel/HIFI molecular line survey of Sagittarius B2(N)

A sensitive broadband molecular line survey of the Sagittarius B2(N) star-forming region has been obtained with the HIFI instrument on the Herschel Space Observatory, offering the first high-spectral resolution look at this well-studied source in a wavelength region largely inaccessible from the ground (625-157 um). From the roughly 8,000 spectral features in the survey, a total of 72 isotopologues arising from 44 different molecules have been identified, ranging from light hydrides to complex organics, and arising from a variety of environments from cold and diffuse to hot and dense gas. We present an LTE model to the spectral signatures of each molecule, constraining the source sizes for hot core species with complementary SMA interferometric observations, and assuming that molecules with related functional group composition are cospatial. For each molecule, a single model is given to fit all of the emission and absorption features of that species across the entire 480-1910 GHz spectral range, accounting for multiple temperature and velocity components when needed to describe the spectrum. As with other HIFI surveys toward massive star forming regions, methanol is found to contribute more integrated line intensity to the spectrum than any other species. We discuss the molecular abundances derived for the hot core, where the local thermodynamic equilibrium approximation is generally found to describe the spectrum well, in comparison to abundances derived for the same molecules in the Orion KL region from a similar HIFI survey.Comment: Accepted to ApJ. 64 pages, 14 figures. Truncated abstrac

Deep soils modify environmental consequences of increased nitrogen fertilizer use in intensifying Amazon agriculture

Agricultural intensification offers potential to grow more food while reducing the conversion of native ecosystems to croplands. However, intensification also risks environmental degradation through emissions of the greenhouse gas nitrous oxide (N2O) and nitrate leaching to ground and surface waters. Intensively-managed croplands and nitrogen (N) fertilizer use are expanding rapidly in tropical regions. We quantified fertilizer responses of maize yield, N2O emissions, and N leaching in an Amazon soybean-maize double-cropping system on deep, highly-weathered soils in Mato Grosso, Brazil. Application of N fertilizer above 80 kg N ha−1 yr−1 increased maize yield and N2O emissions only slightly. Unlike experiences in temperate regions, leached nitrate accumulated in deep soils with increased fertilizer and conversion to cropping at N fertilization rates \u3e80 kg N ha−1, which exceeded maize demand. This raises new questions about the capacity of tropical agricultural soils to store nitrogen, which may determine when and how much nitrogen impacts surface waters

The ratio of means method as an alternative to mean differences for analyzing continuous outcome variables in meta-analysis: A simulation study

<p>Abstract</p> <p>Background</p> <p>Meta-analysis of continuous outcomes traditionally uses mean difference (MD) or standardized mean difference (SMD; mean difference in pooled standard deviation (SD) units). We recently used an alternative ratio of mean values (RoM) method, calculating RoM for each study and estimating its variance by the delta method. SMD and RoM allow pooling of outcomes expressed in different units and comparisons of effect sizes across interventions, but RoM interpretation does not require knowledge of the pooled SD, a quantity generally unknown to clinicians.</p> <p>Objectives and methods</p> <p>To evaluate performance characteristics of MD, SMD and RoM using simulated data sets and representative parameters.</p> <p>Results</p> <p>MD was relatively bias-free. SMD exhibited bias (~5%) towards no effect in scenarios with few patients per trial (n = 10). RoM was bias-free except for some scenarios with broad distributions (SD 70% of mean value) and medium-to-large effect sizes (0.5–0.8 pooled SD units), for which bias ranged from -4 to 2% (negative sign denotes bias towards no effect). Coverage was as expected for all effect measures in all scenarios with minimal bias. RoM scenarios with bias towards no effect exceeding 1.5% demonstrated lower coverage of the 95% confidence interval than MD (89–92% vs. 92–94%). Statistical power was similar. Compared to MD, simulated heterogeneity estimates for SMD and RoM were lower in scenarios with bias because of decreased weighting of extreme values. Otherwise, heterogeneity was similar among methods.</p> <p>Conclusion</p> <p>Simulation suggests that RoM exhibits comparable performance characteristics to MD and SMD. Favourable statistical properties and potentially simplified clinical interpretation justify the ratio of means method as an option for pooling continuous outcomes.</p