Cytokine gene polymorphisms in preterm infants with necrotising enterocolitis: genetic association study

BACKGROUND The inflammatory cytokine cascade is implicated in the pathogenesis of necrotising enterocolitis (NEC). Genetic association studies of cytokine polymorphisms may help to detect molecular mechanisms that are causally related to the disease process. AIM To examine associations between the common genetic variants in candidate inflammatory cytokine genes and NEC in preterm infants. METHODS Multi-centre case-control and genetic association study. DNA samples were collected from 50 preterm infants with NEC and 50 controls matched for gestational age and ethnic group recruited to a multi-centre case-control study. Ten candidate single-nucleotide polymorphisms in cytokines previously associated with infectious or inflammatory diseases were genotyped. The findings were included in random-effects meta-analyses with data from previous genetic association studies. RESULTS All allele distributions were in Hardy-Weinberg equilibrium. None of the studied cytokine polymorphisms was significantly associated with NEC. Four previous genetic association studies of cytokine polymorphisms and NEC in preterm infants were found. Meta-analyses were possible for several single-nucleotide polymorphisms. These increased the precision of the estimates of effect size but did not reveal any significant associations. CONCLUSIONS The available data are not consistent with more than modest associations between these candidate cytokine variant alleles and NEC in preterm infants. Data from future association studies of these polymorphisms may be added to the meta-analyses to obtain more precise estimates of effects sizes.The study was funded by Tenovus (Scotland)

Are difficulties in mentalizing associated with severity of Antisocial Personality Disorder?

Part 1 of the thesis reviews the literature on the measurement of mentalization in adult clinical populations. As mentalization is a broad multi-faceted term, the search incorporates the related concepts of Theory of Mind (ToM) and Emotional Intelligence (EI) as these have been widely operationalised. The review presents a framework for different types of measures, including performance-based tasks and self-report questionnaires, and considers their relative psychometric strengths. It finds an absence of any one measure that covers the breadth of the mentalization construct, however, a set of recommendations are made for an optimal approach using currently available tools. Part 2 presents an empirical study of the relationship between mentalizing capability and severity of Antisocial Personality Disorder (ASPD) in an offender sample. The results show that some specific mentalizing measures were able to modestly predict severity of ASPD. These were the ability to take the perspective of another person, the ability to read mental states from the ‘eyes’ and a general inability to mentalize. These findings suggest that a greater understanding of mentalizing capacities in people with ASPD may support improved risk assessment and clinical treatments. The study’s limitations are considered and its implications for further research and practice. Part 3 presents a critical appraisal of the process of undertaking this research. It describes some of the challenges to joint working across the NHS and the Criminal Justice System. It considers how the use of psychometric assessment can be improved in an ASPD/offender population. It builds on the literature review to recommend how the operationalisation of mentalization can be further enhanced

Understanding non-vaccinating parents' views to inform and improve clinical encounters: A qualitative study in an Australian community

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objectives To explain vaccination refusal in a sample of Australian parents. Design Qualitative design, purposive sampling in a defined population. Setting A geographically bounded community of approximately 30 000 people in regional Australia with high prevalence of vaccination refusal. Participants Semi structured interviews with 32 non-vaccinating parents: 9 fathers, 22 mothers and 1 pregnant woman. Purposive sampling of parents who had decided to discontinue or decline all vaccinations for their children. Recruitment via local advertising then snowballing. Results Thematic analysis focused on explaining decision-making pathways of parents who refuse vaccination. Common patterns in parents' accounts included: perceived deterioration in health in Western societies; a personal experience introducing doubt about vaccine safety; concerns regarding consent; varied encounters with health professionals (dismissive, hindering and helpful); a quest for the real truth'; reactance to system inflexibilities and ongoing risk assessment. Conclusions We suggest responses tailored to the perspectives of non-vaccinating parents to assist professionals in understanding and maintaining empathic clinical relationships with this important patient group

Amino acid changes in the spike protein of feline coronavirus correlate with systemic spread of virus from the intestine and not with feline infectious peritonitis

Recent evidence suggests that a mutation in the spike protein gene of feline coronavirus (FCoV), which results in an amino acid change from methionine to leucine at position 1058, may be associated with feline infectious peritonitis (FIP). Tissue and faecal samples collected post mortem from cats diagnosed with or without FIP were subjected to RNA extraction and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to detect FCoV RNA. In cats with FIP, 95% of tissue, and 81% of faecal samples were PCR-positive, as opposed to 22% of tissue, and 60% of faecal samples in cats without FIP. Relative FCoV copy numbers were significantly higher in the cats with FIP, both in tissues (P < 0.001) and faeces (P = 0.02). PCR-positive samples underwent pyrosequencing encompassing position 1058 of the FCoV spike protein. This identified a methionine codon at position 1058, consistent with the shedding of an enteric form of FCoV, in 77% of the faecal samples from cats with FIP, and in 100% of the samples from cats without FIP. In contrast, 91% of the tissue samples from cats with FIP and 89% from cats without FIP had a leucine codon at position 1058, consistent with a systemic form of FCoV. These results suggest that the methionine to leucine substitution at position 1058 in the FCoV spike protein is indicative of systemic spread of FCoV from the intestine, rather than a virus with the potential to cause FIP

Identifying circumstances under which high insecticide dose increases or decreases resistance selection

Insect management strategies for agricultural crop pests must reduce selection for insecticide resistant mutants while providing effective control of the insect pest. One management strategy that has long been advocated is the application of insecticides at the maximum permitted dose. This has been found, under some circumstances, to be able to prevent the resistance allele frequency from increasing. However this approach may, under different circumstances, lead to rapid selection for resistance to the insecticide. To test when a high dose would be an effective resistance management strategy, we present a flexible deterministic model of a population of an insect pest of agricultural crops. The model includes several possible life-history traits including sexual or asexual reproduction, diploid or haplodiploid genetics, univoltine or multivoltine life cycle, so that the high dose strategy can be tested for many different insect pests. Using this model we aim to identify the key characteristics of pests that make either a high dose or a low dose of insecticide optimal for resistance management. Two outputs are explored: firstly whether the frequency of the resistance allele increases over time or remains low indefinitely; and secondly whether lowering the dose of insecticide applied reduces or increases the rate of selection for the resistance allele. It is demonstrated that with high immigration resistance can be suppressed. This suppression however, is rarely lost if the insecticide dose is reduced, and is absent altogether when individuals move from the treated population back into an untreated population. Reducing the dose of insecticide often resulted in slower development of resistance, except where the population combined a high influx of less resistant individuals into the treated population, a recessive resistance gene and a high efficacy, in which case reducing the dose of insecticide could result in faster selection for resistance

Defining Integrated Weed Management: A Novel Conceptual Framework for Models

Weed population dynamics models are an important tool for predicting the outcome of alternative Integrated Weed Management (IWM) scenarios. The growing problem of herbicide resistance has increased the urgency for these tools in the design of sustainable IWM solutions. We developed a conceptual framework for defining IWM as a standardised input template to allow output from different models to be compared and to design IWM scenarios. The framework could also be used as a quantitative metric to determine whether more diverse systems are more sustainable and less vulnerable to herbicide resistance using empirical data. Using the logic of object-oriented programming, we defined four classes of weed management options based on the stage in the weed life cycle that they impact and processes that mediate their effects. Objects in the same class share a common set of properties that determine their behaviour in weed population dynamics models. Any weed control “event” in a system is associated with an object, meaning alternative management scenarios can be built by systematically adding events to a model either to compare existing systems or design novel approaches. Our framework is designed to be generic, allowing IWM systems from different cropping systems and countries to be compared

Offenders With Antisocial Personality Disorder Display More Impairments in Mentalizing

This study was designed to test the hypothesis that individuals with antisocial, particularly violent, histories of offending behavior have specific problems in social cognition, notably in relation to accurately envisioning mental states. Eighty-three male offenders on community license, 65% of whom met the threshold for antisocial personality disorder (ASPD), completed a battery of computerized mentalizing tests requiring perspective taking (Perspectives Taking Test), mental state recognition from facial expression (Reading the Mind in the Eyes Test), and identification of mental states in the context of social interaction (Movie for the Assessment of Social Cognition). The results were compared with a partially matched sample of 42 nonoffending controls. The offender group showed impaired mentalizing on all of the tasks when compared with the control group for this study when controlling for demographic and clinical variables, and the offending group performed poorly in comparisons with participants in published studies, suggesting that limited capacity to mentalize may be part of the picture presented by individuals with histories of offending behavior. Offenders with ASPD demonstrated greater difficulty with mentalizing than non-ASPD offenders. Mentalization subscales were able to predict offender status and those with ASPD, indicating that specific impairments in perspective taking, social cognition, and social sensitivity, as well as tendencies toward hypomentalizing and nonmentalizing, are more marked in individuals who meet criteria for a diagnosis of ASPD. Awareness of these deficits may be helpful to professionals working with offenders, and specifically addressing these deficits may be a productive aspect of therapy for this "hard to reach" clinical group