Hypothalamic actions of neuromedin U.

The central nervous system and gut peptide neuromedin U (NMU) inhibits feeding after intracerebroventricular injection. This study explored the hypothalamic actions of NMU on feeding and the hypothalamo-pituitary-adrenal axis. Intraparaventricular nucleus (intra-PVN) NMU dose-dependently inhibited food intake, with a minimum effective dose of 0.1 nmol and a robust effect at 0.3 nmol. Feeding inhibition was mapped by NMU injection into eight hypothalamic areas. NMU (0.3 nmol) inhibited food intake in the PVN (0-1 h, 59 ± 6.9% of the control value; P < 0.001) and arcuate nucleus (0-1 h, 76 ± 10.4% of the control value; P < 0.05). Intra-PVN NMU markedly increased grooming and locomotor behavior and dose-dependently increased plasma ACTH (0.3 nmol NMU, 24.8 ± 1.9 pg/ml; saline, 11.4 ± 1.0; P < 0.001) and corticosterone (0.3 nmol NMU, 275.4 ± 40.5 ng/ml; saline, 129.4 ± 25.0; P < 0.01). Using hypothalamic explants in vitro, NMU stimulated CRH (100 nM NMU, 5.9 ± 0.95 pmol/explant; basal, 3.8 ± 0.39; P < 0.01) and arginine vasopressin release (100 nM NMU, 124.5 ± 21.8 fmol/explant; basal, 74.5 ± 7.6; P < 0.01). Leptin stimulated NMU release (141.9 ± 20.4 fmol/explant; basal, 92.9 ± 9.4; P < 0.01). Thus, we describe a novel role for NMU in the PVN to stimulate the hypothalamo-pituitary-adrenal axis and locomotor and grooming behavior and to inhibit feeding

Needle Tip Force Estimation using an OCT Fiber and a Fused convGRU-CNN Architecture

Needle insertion is common during minimally invasive interventions such as biopsy or brachytherapy. During soft tissue needle insertion, forces acting at the needle tip cause tissue deformation and needle deflection. Accurate needle tip force measurement provides information on needle-tissue interaction and helps detecting and compensating potential misplacement. For this purpose we introduce an image-based needle tip force estimation method using an optical fiber imaging the deformation of an epoxy layer below the needle tip over time. For calibration and force estimation, we introduce a novel deep learning-based fused convolutional GRU-CNN model which effectively exploits the spatio-temporal data structure. The needle is easy to manufacture and our model achieves a mean absolute error of 1.76 +- 1.5 mN with a cross-correlation coefficient of 0.9996, clearly outperforming other methods. We test needles with different materials to demonstrate that the approach can be adapted for different sensitivities and force ranges. Furthermore, we validate our approach in an ex-vivo prostate needle insertion scenario.Comment: Accepted for Publication at MICCAI 201

Laser Generation of Narrow Band Ultrasound

Laser based sensor systems to replace conventional piezoelectric contact transducers for ultrasonic testing continue under development for applications where contact with the specimen surface is undesirable or impossible. To date, such systems are considerably less sensitive than their piezoelectric counterparts. As a result, a great deal of effort has contributed to the development of a number of interferoroetric transducer systems to detect ultrasound. Increasingly, however, researchers have begun looking at laser ultrasonic sources to see what improvements might be made to enhance overall system sensitivity for laser generation and detection of ultrasound

CASTNet: Community-Attentive Spatio-Temporal Networks for Opioid Overdose Forecasting

Opioid overdose is a growing public health crisis in the United States. This crisis, recognized as "opioid epidemic," has widespread societal consequences including the degradation of health, and the increase in crime rates and family problems. To improve the overdose surveillance and to identify the areas in need of prevention effort, in this work, we focus on forecasting opioid overdose using real-time crime dynamics. Previous work identified various types of links between opioid use and criminal activities, such as financial motives and common causes. Motivated by these observations, we propose a novel spatio-temporal predictive model for opioid overdose forecasting by leveraging the spatio-temporal patterns of crime incidents. Our proposed model incorporates multi-head attentional networks to learn different representation subspaces of features. Such deep learning architecture, called "community-attentive" networks, allows the prediction of a given location to be optimized by a mixture of groups (i.e., communities) of regions. In addition, our proposed model allows for interpreting what features, from what communities, have more contributions to predicting local incidents as well as how these communities are captured through forecasting. Our results on two real-world overdose datasets indicate that our model achieves superior forecasting performance and provides meaningful interpretations in terms of spatio-temporal relationships between the dynamics of crime and that of opioid overdose.Comment: Accepted as conference paper at ECML-PKDD 201

Dual Oxidase Maturation factor 1 (DUOXA1) overexpression increases reactive oxygen species production and inhibits murine muscle satellite cell differentiation

Background: Dual oxidase maturation factor 1 (DUOXA1) has been associated with the maturation of the reactive oxygen species (ROS) producing enzyme, dual oxidase 1 (DUOX1) in the adult thyroid. However, ROS have also been implicated in the development of several tissues. We found that activated muscle satellite cells and primary myoblasts isolated from mice express robust levels of DUOXA1 and that its levels are altered as cells differentiate. Results: To determine whether DUOXA1 levels affect muscle differentiation, we used an adenoviral construct (pCMV5-DUOXA1-GFP) to drive constitutive overexpression of this protein in primary myoblasts. High levels of DUOXA1 throughout myogenesis resulted in enhanced H2O2 production, fusion defects, reduced expression of early (myogenin) and late (myosin heavy chain) markers of differentiation, and elevated levels of apoptosis compared to control cells infected with an empty adenoviral vector (pCMV5-GFP). DUOXA1 knockdown (using a DUOXA1 shRNA construct) resulted in enhanced differentiation compared to cells subjected to a control shRNA, and subjecting DUOXA1 overexpressing cells to siRNAs targeting DUOX1 or apoptosis signal-regulating kinase 1 (ASK1) rescued the phenotype. Conclusions: This study represents the first to demonstrate the importance of DUOXA1 in skeletal muscle myoblasts and that DUOXA1 overexpression in muscle stem cells induces apoptosis and inhibits differentiation through DUOX1 and ASK1. © 2014 Sandiford et al.; licensee BioMed Central Ltd

Dual Oxidase Maturation factor 1 (DUOXA1) overexpression increases reactive oxygen species production and inhibits murine muscle satellite cell differentiation

Background: Dual oxidase maturation factor 1 (DUOXA1) has been associated with the maturation of the reactive oxygen species (ROS) producing enzyme, dual oxidase 1 (DUOX1) in the adult thyroid. However, ROS have also been implicated in the development of several tissues. We found that activated muscle satellite cells and primary myoblasts isolated from mice express robust levels of DUOXA1 and that its levels are altered as cells differentiate. Results: To determine whether DUOXA1 levels affect muscle differentiation, we used an adenoviral construct (pCMV5-DUOXA1-GFP) to drive constitutive overexpression of this protein in primary myoblasts. High levels of DUOXA1 throughout myogenesis resulted in enhanced H2O2 production, fusion defects, reduced expression of early (myogenin) and late (myosin heavy chain) markers of differentiation, and elevated levels of apoptosis compared to control cells infected with an empty adenoviral vector (pCMV5-GFP). DUOXA1 knockdown (using a DUOXA1 shRNA construct) resulted in enhanced differentiation compared to cells subjected to a control shRNA, and subjecting DUOXA1 overexpressing cells to siRNAs targeting DUOX1 or apoptosis signal-regulating kinase 1 (ASK1) rescued the phenotype. Conclusions: This study represents the first to demonstrate the importance of DUOXA1 in skeletal muscle myoblasts and that DUOXA1 overexpression in muscle stem cells induces apoptosis and inhibits differentiation through DUOX1 and ASK1. © 2014 Sandiford et al.; licensee BioMed Central Ltd

Lattice QCD without topology barriers

As the continuum limit is approached, lattice QCD simulations tend to get trapped in the topological charge sectors of field space and may consequently give biased results in practice. We propose to bypass this problem by imposing open (Neumann) boundary conditions on the gauge field in the time direction. The topological charge can then flow in and out of the lattice, while many properties of the theory (the hadron spectrum, for example) are not affected. Extensive simulations of the SU(3) gauge theory, using the HMC and the closely related SMD algorithm, confirm the absence of topology barriers if these boundary conditions are chosen. Moreover, the calculated autocorrelation times are found to scale approximately like the square of the inverse lattice spacing, thus supporting the conjecture that the HMC algorithm is in the universality class of the Langevin equation.Comment: Plain TeX source, 26 pages, 4 figures include

Dietary nitrate modulates cerebral blood flow parameters and cognitive performance in humans: A double-blind, placebo-controlled, crossover investigation.

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Nitrate derived from vegetables is consumed as part of a normal diet and is reduced endogenously via nitrite to nitric oxide. It has been shown to improve endothelial function, reduce blood pressure and the oxygen cost of sub-maximal exercise, and increase regional perfusion in the brain. The current study assessed the effects of dietary nitrate on cognitive performance and prefrontal cortex cerebral blood-flow (CBF) parameters in healthy adults. In this randomised, double-blind, placebo-controlled, parallel-groups study, 40 healthy adults received either placebo or 450 ml beetroot juice (~5.5 mmol nitrate). Following a 90 minute drink/absorption period, participants performed a selection of cognitive tasks that activate the frontal cortex for 54 min. Near-Infrared Spectroscopy (NIRS) was used to monitor CBF and hemodynamics, as indexed by concentration changes in oxygenated and deoxygenated-haemoglobin, in the frontal cortex throughout. The bioconversion of nitrate to nitrite was confirmed in plasma by ozone-based chemi-luminescence. Dietary nitrate modulated the hemodynamic response to task performance, with an initial increase in CBF at the start of the task period, followed by consistent reductions during the least demanding of the three tasks utilised. Cognitive performance was improved on the serial 3s subtraction task. These results show that single doses of dietary nitrate can modulate the CBF response to task performance and potentially improve cognitive performance, and suggest one possible mechanism by which vegetable consumption may have beneficial effects on brain function

Methodological bias in cluster randomised trials

Background: Cluster randomised trials can be susceptible to a range of methodological problems. These problems are not commonly recognised by many researchers. In this paper we discuss the issues that can lead to bias in cluster trials. Methods: We used a sample of cluster randomised trials from a recent review and from a systematic review of hip protectors. We compared the mean age of participants between intervention groups in a sample of 'good' cluster trials with a sample of potentially biased trials. We also compared the effect sizes, in a funnel plot, between hip protector trials that used individual randomisation compared with those that used cluster randomisation. Results: There is a tendency for cluster trials, with evidence methodological biases, to also show an age imbalance between treatment groups. In a funnel plot we show that all cluster trials show a large positive effect of hip protectors whilst individually randomised trials show a range of positive and negative effects, suggesting that cluster trials may be producing a biased estimate of effect. Conclusion: Methodological biases in the design and execution of cluster randomised trials is frequent. Some of these biases associated with the use of cluster designs can be avoided through careful attention to the design of cluster trials. Firstly, if possible, individual allocation should be used. Secondly, if cluster allocation is required, then ideally participants should be identified before random allocation of the clusters. Third, if prior identification is not possible, then an independent recruiter should be used to recruit participants

Activating KIR2DS4 Is Expressed by Uterine NK Cells and Contributes to Successful Pregnancy

Tissue-specific NK cells are abundant in the pregnant uterus and interact with invading placental trophoblast cells that transform the maternal arteries to increase the fetoplacental blood supply. Genetic case-control studies have implicated killer cell Ig-like receptor (KIR) genes and their $\textit{HLA}$ ligands in pregnancy disorders characterized by failure of trophoblast arterial transformation. Activating $\textit{KIR2DS1}$ or $\textit{KIR2DS5}$ (when located in the centromeric region as in Africans) lower the risk of disorders when there is a fetal $\textit{HLA-C}$ allele carrying a C2 epitope. In this study, we investigated another activating $\textit{KIR, KIR2DS4}$, and provide genetic evidence for a similar effect when carried with $\textit{KIR2DS1. KIR2DS4}$ is expressed by ∼45% of uterine NK (uNK) cells. Similarly to KIR2DS1, triggering of KIR2DS4 on uNK cells led to secretion of GM-CSF and other chemokines, known to promote placental trophoblast invasion. Additionally, XCL1 and CCL1, identified in a screen of 120 different cytokines, were consistently secreted upon activation of KIR2DS4 on uNK cells. Inhibitory $\textit{KIR2DL5A}$, carried in linkage disequilibrium with $\textit{KIR2DS1}$, is expressed by peripheral blood NK cells but not by uNK cells, highlighting the unique phenotype of uNK cells compared with peripheral blood NK cells. That KIR2DS4, KIR2DS1, and some alleles of KIR2DS5 contribute to successful pregnancy suggests that activation of uNK cells by KIR binding to HLA-C is a generic mechanism promoting trophoblast invasion into the decidua.This work was supported by the Wellcome Trust, the Centre for Trophoblast Research, the British Heart Foundation, and the Cambridge Philosophical Society