A focus on cross-purpose tools, automated recognition of study design in multiple disciplines, and evaluation of automation tools: a summary of significant discussions at the fourth meeting of the International Collaboration for Automation of Systematic Reviews (ICASR)

The fourth meeting of the International Collaboration for Automation of Systematic Reviews (ICASR) was held 5–6 November 2019 in The Hague, the Netherlands. ICASR is an interdisciplinary group whose goal is to maximize the use of technology for conducting rapid, accurate, and efficient systematic reviews of scientific evidence. The group seeks to facilitate the development and acceptance of automated techniques for systematic reviews. In 2018, the major themes discussed were the transferability of automation tools (i.e., tools developed for other purposes that might be used by systematic reviewers), the automated recognition of study design in multiple disciplines and applications, and approaches for the evaluation of automation tools

The Yin and Yang of Nicotine: Harmful during Development, Beneficial in Adult Patient Populations

Nicotine has remarkably diverse effects on the brain. Being the main active compound in tobacco, nicotine can aversively affect brain development. However, it has the ability to act positively by restoring attentional capabilities in smokers. Here, we focus on nicotine exposure during the prenatal and adolescent developmental periods and specifically, we will review the long-lasting effects of nicotine on attention, both in humans and animal models.We discuss the reciprocal relation of the beneficial effects of nicotine, improving attention in smokers and in patients with neuropsychiatric diseases, such as schizophrenia and attention deficit/hyperactivity disorder, vs. nicotine-related attention deficits already caused during adolescence. Given the need for research on the mechanisms of nicotine's cognitive actions, we discuss some of the recent work performed in animals. © 2012 Counotte, Smit and Spijker

Feasibility of using teleradiology to improve tuberculosis screening and case management in a district hospital in Malawi.

Malawi has one of the world's highest rates of human immunodeficiency virus (HIV) infection (10.6%), and southern Malawi, where Thyolo district is located, bears the highest burden in the country (14.5%). Tuberculosis, common among HIV-infected people, requires radiologic diagnosis, yet Malawi has no radiologists in public service. This hinders rapid and accurate diagnosis and increases morbidity and mortality

Profiling gene expression in whole blood samples following an in-vitro challenge

Genomics tools (gene- and protein-expression studies) can be used to find possible target genes involved in a quantifiable trait or disease state. However in many instances, cells and tissues directly involved in the trait's expression, for example, brain tissue, are not amenable for gene expression analysis. Whole blood cells share a molecular make-up for cellular communication and gene regulation systems with many other cell types, for example, neuronal cells, and have the advantage of being very accessible for gene profiling. We investigated the feasibility of nationwide blood sample collection for lymphocyte RNA isolation and real-time PCR analysis to quantify genomic responses. We tested several designs for blood collection and storage: blood sampling in PAXgene blood collection tubes and storage at -20°C, blood sampling in heparin tubes and decanting the samples (with or without in-vitro stimulus) into either PAXgene blood collection tubes and storage at -20°C, or polypropylene tubes followed by snap-freezing and storage at -80°C. The latter procedure is the best cost-wise when only small amounts of total RNA are needed for downstream applications. Lymphocyte gene expression studies are most likely hampered by the quality of isolated RNA rather than the sampling method. We show that large-scale nationwide sample collections did not alter RNA quality or gene expression levels when compared to sampling and processing in a more controlled way. To this end, we present an optimized protocol for easy and standardized isolation of high quality RNA using the PAXgene isolation kit. Based on these results, we suggest that whole blood genomic data can be used as a genomic probe in experimental and clinical research

GABAergic Synapse Properties May Explain Genetic Variation in Hippocampal Network Oscillations in Mice

Cognitive ability and the properties of brain oscillation are highly heritable in humans. Genetic variation underlying oscillatory activity might give rise to differences in cognition and behavior. How genetic diversity translates into altered properties of oscillations and synchronization of neuronal activity is unknown. To address this issue, we investigated cellular and synaptic mechanisms of hippocampal fast network oscillations in eight genetically distinct inbred mouse strains. The frequency of carbachol-induced oscillations differed substantially between mouse strains. Since GABAergic inhibition sets oscillation frequency, we studied the properties of inhibitory synaptic inputs (IPSCs) received by CA3 and CA1 pyramidal cells of three mouse strains that showed the highest, lowest and intermediate frequencies of oscillations. In CA3 pyramidal cells, the frequency of rhythmic IPSC input showed the same strain differences as the frequency of field oscillations. Furthermore, IPSC decay times in both CA1 and CA3 pyramidal cells were faster in mouse strains with higher oscillation frequencies than in mouse strains with lower oscillation frequency, suggesting that differences in GABAA-receptor subunit composition exist between these strains. Indeed, gene expression of GABAA-receptor β2 (Gabrb2) and β3 (Gabrb2) subunits was higher in mouse strains with faster decay kinetics compared with mouse strains with slower decay kinetics. Hippocampal pyramidal neurons in mouse strains with higher oscillation frequencies and faster decay kinetics fired action potential at higher frequencies. These data indicate that differences in genetic background may result in different GABAA-receptor subunit expression, which affects the rhythm of pyramidal neuron firing and fast network activity through GABA synapse kinetics

Evaluation of a chest radiograph reading and recording system for tuberculosis in a HIV-positive cohort.

Aim To assess the impact of introducing a chest radiograph reading and recording system (CRRS) with a short training session, on the accuracy and inter-reader variability of tuberculosis (TB) interpretation of chest radiographs (CXRs) by a group of non-expert readers in a human immunodeficiency virus (HIV)-positive cohort. Materials and methods A set of 139 CXRs was reviewed by a group of eight physicians pre- and post-intervention at two clinics in Shan State, Myanmar, providing HIV/TB diagnosis and treatment services. The results were compared against the consensus of expert radiologists for accuracy. Results Overall accuracy was similar pre- and post-intervention for most physicians with an average area under the receiver operating characteristic curve difference of 0.02 (95% confidence interval: –0.03, 0.07). The overall agreement among physicians was poor pre- and post-intervention (Fleiss κ=0.35 and κ=0.29 respectively). The assessment of agreement for specific disease patterns associated with active TB in HIV-infected patients showed that for intrinsically subtle findings, the agreement was generally poor but better for the more intrinsically obvious disease patterns: pleural effusion (Cohen’s kappa range = 0.37–0.67) and milliary nodular pattern (Cohen’s kappa range = 0.25–0.52). Conclusion This study demonstrated limited impact of the introduction of a CRRS on CXR accuracy and agreement amongst non-expert readers. The role in which CXRs are used for TB diagnosis in a HIV-positive cohort in similar clinical contexts should be reviewed

Evidence for enhanced neurobehavioral vulnerability to nicotine during periadolescence in rats

Epidemiological studies indicate that there is an increased likelihood for the development of nicotine addiction when cigarette smoking starts early during adolescence. These observations suggest that adolescence could be a “critical ” ontogenetic period, during which drugs of abuse have distinct effects responsible for the development of dependence later in life. We compared the long-term behavioral and molecular effects of repeated nicotine treatment during either periadolescence or postadolescence in rats. It was found that exposure to nicotine during periadolescence, but not a similar exposure in the postadolescent period, increased the intravenous self-administration of nicotine and the expression of distinct subunits of the ligand-gated acetylcholine receptor in adult animals. Both these changes indicated an increased sensitivity to the addictive properties of nicotine. In conclusion, adolescence seems to be a critical developmental period, characterized by enhanced neurobehavioral vulnerability to nicotine. Key words: nicotine; adolescence; intravenous; self-administration; acetylcholine receptor; PC

The importance of stakeholders in scoping risk assessments—Lessons from low-carbon transitions

Identifying the risks that could impact a low-carbon transition is a prerequisite to assessing and managing these risks. We systematically characterise risks associated with decarbonisation pathways in fifteen case studies conducted in twelve countries around the world. We find that stakeholders from business, government, NGOs, and others supplied some 40 % of these risk inputs, significantly widening the scope of risks considered by academics and experts. Overall, experts and academics consider more economic risks and assess these with quantitative methods and models, while other stakeholders consider political risks more. To avoid losing sight of risks that cannot be easily quantified and modelled, including some economic risks, impact assessment modelling should be complemented with qualitative research and active stakeholder engagement. A systematic risk elicitation facilitates communication with stakeholders, enables better risk mitigation, and increases the chance of a sustainable transition