Evaluation of bioluminescence-based assays of anti-malarial drug activity

Transgenic Plasmodium falciparum expressing luciferase offers an attractive bioluminescence-based assay platform for the investigation of the pharmacological properties of anti-malarial drugs. Here a side-by-side comparison of bioluminescence and fluorescence-based assays, utilizing a luciferase reporter cassette that confers a strong temporal pattern of luciferase expression during the S-phase of intraerythrocytic development, is reported

Automated Synthesis of Tableau Calculi

This paper presents a method for synthesising sound and complete tableau calculi. Given a specification of the formal semantics of a logic, the method generates a set of tableau inference rules that can then be used to reason within the logic. The method guarantees that the generated rules form a calculus which is sound and constructively complete. If the logic can be shown to admit finite filtration with respect to a well-defined first-order semantics then adding a general blocking mechanism provides a terminating tableau calculus. The process of generating tableau rules can be completely automated and produces, together with the blocking mechanism, an automated procedure for generating tableau decision procedures. For illustration we show the workability of the approach for a description logic with transitive roles and propositional intuitionistic logic.Comment: 32 page

Implementing a 48 h EWTD-compliant rota for junior doctors in the UK does not compromise patients’ safety : assessor-blind pilot comparison

Background: There are currently no field data about the effect of implementing European Working Time Directive (EWTD)-compliant rotas in a medical setting. Surveys of doctors’ subjective opinions on shift work have not provided reliable objective data with which to evaluate its efficacy. Aim: We therefore studied the effects on patient's safety and doctors’ work-sleep patterns of implementing an EWTD-compliant 48 h work week in a single-blind intervention study carried out over a 12-week period at the University Hospitals Coventry & Warwickshire NHS Trust. We hypothesized that medical error rates would be reduced following the new rota. Methods: Nineteen junior doctors, nine studied while working an intervention schedule of <48 h per week and 10 studied while working traditional weeks of <56 h scheduled hours in medical wards. Work hours and sleep duration were recorded daily. Rate of medical errors (per 1000 patient-days), identified using an established active surveillance methodology, were compared for the Intervention and Traditional wards. Two senior physicians blinded to rota independently rated all suspected errors. Results: Average scheduled work hours were significantly lower on the intervention schedule [43.2 (SD 7.7) (range 26.0–60.0) vs. 52.4 (11.2) (30.0–77.0) h/week; P < 0.001], and there was a non-significant trend for increased total sleep time per day [7.26 (0.36) vs. 6.75 (0.40) h; P = 0.095]. During a total of 4782 patient-days involving 481 admissions, 32.7% fewer total medical errors occurred during the intervention than during the traditional rota (27.6 vs. 41.0 per 1000 patient-days, P = 0.006), including 82.6% fewer intercepted potential adverse events (1.2 vs. 6.9 per 1000 patient-days, P = 0.002) and 31.4% fewer non-intercepted potential adverse events (16.6 vs. 24.2 per 1000 patient-days, P = 0.067). Doctors reported worse educational opportunities on the intervention rota. Conclusions: Whilst concerns remain regarding reduced educational opportunities, our study supports the hypothesis that a 48 h work week coupled with targeted efforts to improve sleep hygiene improves patient safety

The Mineral Composition of Wild Type and Cultivated Varieties of Pasture Species

Mineral deficiencies in livestock are often prevented by using prophylactic supplementation, which is imprecise and inefficient. Instead, the trend for increased species diversity in swards is an opportunity to improve mineral concentrations in the basal diet. Currently there are limited data on the mineral concentrations of different species and botanical groups, particularly for I and Se, which are among the most deficient minerals in livestock diets. We grew 21 pasture species, including some cultivar/wild type comparisons, of grasses, legumes and forbs, as single species stands in a pot study in a standard growth medium. Herbage concentrations of Co, Cu, I, Mn, Se, Zn, S, Mo and Fe showed no consistent differences between the wild and cultivated types. There were significant differences between botanical groups for many minerals tested. Forbs were highest in I and Se, grasses in Mn, and legumes in Cu, Co, Zn and Fe. Comparing species concentrations to recommended livestock intakes, the forbs Achillea millefolium, Cichorium intybus and Plantago lanceolate, and the legumes Medicago lupulina, Trifolium hybridum, and Lotus corniculatus, appear good sources of Co, Cu, I, Se and Zn. Further work is required to ensure these results are consistent in multispecies mixtures, in different soil types, and in field trials

Application of monoclonal antibodies in quantifying fungal growth dynamics during aerobic spoilage of silage

Proliferation of filamentous fungi following ingress of oxygen to silage is an important cause of dry matter losses, resulting in significant waste. In addition, the production of mycotoxins by some filamentous fungi pose a risk to animal health through mycotoxicosis. Quantitative assessment of fungal growth in silage, through measurement of ergosterol content, colony forming units or temperature increase are limiting in representing fungal growth dynamics during aerobic spoilage due to being deficient in either representing fungal biomass or being able to identify specific genera. Here, we conducted a controlled environment aerobic exposure experiment to test the efficacy of a monoclonal antibody-based enzyme linked immunosorbent assay (ELISA) to detect the proliferation of fungal biomass in six silage samples. We compared this to temperature which has been traditionally deployed in such experiments and on-farm to detect aerobic deterioration. In addition, we quantified ergosterol, a second marker of fungal biomass. At 8 d post aerobic exposure, the ergosterol and ELISA methods indicated an increase in fungal biomass in one of the samples with a temperature increase observed after 16 d. A comparison of the methods with Pearson’s correlation coefficient showed a positive association between temperature and ergosterol and both markers of fungal biomass. This work indicates that the technology has potential to be used as an indicator of microbial degradation in preserved forage. Consequently, if developed as an on farm technique this could inform forage management decisions made by farmers, with the goal of decreasing dry matter losses, improving resource and nutrient efficiency and reducing risks to animal health

Arithmetically Cohen-Macaulay Bundles on complete intersection varieties of sufficiently high multidegree

Recently it has been proved that any arithmetically Cohen-Macaulay (ACM) bundle of rank two on a general, smooth hypersurface of degree at least three and dimension at least four is a sum of line bundles. When the dimension of the hypersurface is three, a similar result is true provided the degree of the hypersurface is at least six. We extend these results to complete intersection subvarieties by proving that any ACM bundle of rank two on a general, smooth complete intersection subvariety of sufficiently high multi-degree and dimension at least four splits. We also obtain partial results in the case of threefolds.Comment: 15 page

An electronic clinical decision support system for the assessment and management of suicidality in primary care: protocol for a mixed-methods study

Background: Suicide is a global public health concern, but it is preventable. Increased contact with primary care before the suicide or attempted suicide raises opportunities for intervention and prevention. However, suicide assessment and management are areas that many general practitioners (GPs) find particularly challenging. Previous research has indicated significant variability in how GPs understand, operationalize, and assess suicide risk, which subsequently has an impact on clinical decision making. Clinical decision support systems (CDSS) have been widely implemented across different health care settings, including primary care to support practitioners in clinical decision making. A CDSS may reduce inconsistencies in the identification, assessment, and management of suicide risk by GPs by guiding them through the consultation and generating a risk assessment plan that can be shared with a service user or with specialized mental health services. Objective: Our aim is to co-develop and test with end users (eg, GPs, primary care attendees, mental health professionals) an electronic clinical decision support system (e-CDSS) to support GPs in the identification, assessment, and management of suicidality in primary care. Methods: Ours is an ongoing embedded mixed-methods study with four phases: (1) qualitative interviews with GPs to explore their views on the content, format, and use of the e-CDSS, as well as consultation with two service-user advisory groups (people aged ≤25 and people aged ≥25) to inform the content of the e-CDSS including phrasing of items and clarity; (2) participatory co-production workshops with GPs, service users, and clinical experts in suicidality to determine the content and format of the e-CDDS; gain consensus of the relevance of items; establish content validity and identify pathways to implementation, using the Consolidated Framework for Implementation Research; (3) building the e-CDSS so that it guides the GP through a consultation; and (4) usability testing of the e-CDSS with GPs and service users in one primary care practice involving a nonlive and a live stage. Results: The study was funded for four years, to take place between 2015 and 2019, and is currently completing phase 4 data collection. The first results are expected to be submitted for publication in June 2019. The findings will enable us to evaluate the feasibility, acceptability, and usability of a suicide-specific, electronic, guided decision support system in primary care. Conclusions: This study will be the first to explore the feasibility, acceptability, and usability of an electronic, guided decision support system for use in primary care consultations for the improved assessment and management of suicidality

Cataract, abnormal electroretinogram and visual evoked potentials in a child with SMA-LED2 - extending the phenotype.

This case report describes a girl who presented antenatal arthrogryposis and postnatal hypotonia, generalized and respiratory weakness, joint deformities particularly affecting the lower limbs and poor swallow. By 5 months, cataracts, abnormal electroretinograms, visual evoked potentials and global developmental impairments were recognized. No causative variants were identified on targeted gene panels. After her unexpected death at 11 months, gene-agnostic trio whole exome sequencing revealed a likely pathogenic de novo BICD2 missense variant, NM_001003800.1, c.593T>C, p.(Leu198Pro), confirming the diagnosis of spinal muscular atrophy lower extremity predominant type 2 (SMA-LED2). We propose that cataracts and abnormal electroretinograms are novel features of SMA-LED2

Meta-analysis of global livestock urine-derived nitrous oxide emissions from agricultural soils

Nitrous oxide (N2O) is an air pollutant of major environmental concern, with agriculture representing 60% of anthropogenic global N2O emissions. Much of the N2O emissions from livestock production systems result from transformation of N deposited to soil within animal excreta. There exists a substantial body of literature on urine patch N2O dynamics, we aimed to identify key controlling factors influencing N2O emissions and to aid understanding of knowledge gaps to improve GHG reporting and prioritise future research. We conducted an extensive literature review and random effect meta-analysis (using REML) of results to identify key relationships between multiple potential independent factors and global N2O emissions factors (EFs) from urine patches. Mean air temperature, soil pH and ruminant animal species (sheep or cow) were significant factors influencing the EFs reviewed. However, several factors that are known to influence N2O emissions, such as animal diet and urine composition, could not be considered due to the lack of reported data. The review highlighted a widespread tendency for inadequate metadata and uncertainty reporting in the published studies, as well as the limited geographical extent of investigations, which are more often conducted in temperate regions thus far. Therefore, here we give recommendations for factors that are likely to affect the EFs and should be included in all future studies, these include: soil pH and texture; experimental set-up; direct measurement of soil moisture and temperature during the study period; amount and composition of urine applied; animal type and diet; N2O emissions with a measure of uncertainty; data from a control with zero-N application and meteorological data

Ontologies, Mental Disorders and Prototypes

As it emerged from philosophical analyses and cognitive research, most concepts exhibit typicality effects, and resist to the efforts of defining them in terms of necessary and sufficient conditions. This holds also in the case of many medical concepts. This is a problem for the design of computer science ontologies, since knowledge representation formalisms commonly adopted in this field do not allow for the representation of concepts in terms of typical traits. However, the need of representing concepts in terms of typical traits concerns almost every domain of real world knowledge, including medical domains. In particular, in this article we take into account the domain of mental disorders, starting from the DSM-5 descriptions of some specific mental disorders. On this respect, we favor a hybrid approach to the representation of psychiatric concepts, in which ontology oriented formalisms are combined to a geometric representation of knowledge based on conceptual spaces