Determination of a suitable low-dose abdominopelvic CT protocol using model-based iterative reconstruction through cadaveric study.

Introduction: Cadaveric studies provide a means of safely assessing new technologies and optimizing scanning prior to clinical validation. Reducing radiation exposure in a clinical setting can entail incremental dose reductions to avoid missing important clinical findings. The use of cadavers allows assessment of the impact of more substantial dose reductions on image quality. Our aim was to identify a suitable low‐dose abdominopelvic CT protocol for subsequent clinical validation. Methods: Five human cadavers were scanned at one conventional dose and three low‐dose settings. All scans were reconstructed using three different reconstruction algorithms: filtered back projection (FBP), hybrid iterative reconstruction (60% FBP and 40% adaptive statistical iterative reconstruction (ASIR40)), and model‐based iterative reconstruction (MBIR). Two readers rated the image quality both quantitatively and qualitatively. Results: Model‐based iterative reconstruction images had significantly better objective image noise and higher qualitative scores compared with both FBP and ASIR40 images at all dose levels. The greatest absolute noise reduction, between MBIR and FBP, of 34.3 HU (equating to a 68% reduction) was at the lowest dose level. MBIR reduced image noise and improved image quality even in CT images acquired with a mean radiation dose reduction of 62% compared with conventional dose studies reconstructed with ASIR40, with lower levels of objective image noise, superior diagnostic acceptability and contrast resolution, and comparable subjective image noise and streak artefact scores. Conclusion: This cadaveric study demonstrates that MBIR reduces image noise and improves image quality in abdominopelvic CT images acquired with dose reductions of up to 62%

Advanced solid state nano-electrochemical sensors and system for agri 4.0 applications

Global food production needs to increase in order to meet the demands of an ever growing global population. As resources are finite, the most feasible way to meet this demand is to minimize losses and improve efficiency. Regular monitoring of factors like animal health, soil and water quality for example, can ensure that the resources are being used to their maximum efficiency. Existing monitoring techniques however have limitations, such as portability, turnaround time and requirement for additional reagents. In this work, we explore the use of micro- and nano-scale electrode devices, for the development of an electrochemical sensing platform to digitalize a wide range of applications within the agri-food sector. With this platform, we demonstrate the direct electrochemical detection of pesticides, specifically clothianidin and imidacloprid, with detection limits of 0.22 ng/mL and 2.14 ng/mL respectively, and nitrates with a detection limit of 0.2 µM. In addition, interdigitated electrode structures also enable an in-situ pH control technique to mitigate pH as an interference and modify analyte response. This technique is applied to the analysis of monochloramine, a common water disinfectant. Concerning biosensing, the sensors are modified with bio-molecular probes for the detection of both bovine viral diarrhea virus species and antibodies, over a range of 1 ng/mL to 10 µg/mL. Finally, a portable analogue front end electronic reader is developed to allow portable sensing, with control and readout undertaken using a smart phone application. Finally, the sensor chip platform is integrated with these electronics to provide a fully functional end-to-end smart sensor system compatible with emerging Agri-Food digital decision support tools

The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer

Volatility as a concept to understand the impact of stress on the microbiome

The microbiome-gut-brain-axis is a complex phenomenon spanning several dynamic systems in the body which can be parsed at a molecular, cellular, physiological and ecological level. A growing body of evidence indicates that this axis is particularly sensitive to the effects of stress and that it may be relevant to stress resilience and susceptibility. Although stress-induced changes in the composition of the microbiome have been reported, the degree of compositional change over time, which we define as volatility, has not been the subject of in-depth scrutiny. Using a chronic psychosocial stress paradigm in male mice, we report that the volatility of the microbiome significantly correlated with several readouts of the stress response, including behaviour and corticosterone response. We then validated these findings in a second independent group of stressed mice. Additionally, we assessed the relationship between volatility and stress parameters in a cohort of health volunteers who were undergoing academic exams and report similar observations. Finally, we found inter-species similarities in the microbiome stress response on a functional level. Our research highlights the effects of stress on the dynamic microbiome and underscores the informative value of volatility as a parameter that should be considered in all future analyses of the microbiome

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe