Spinally projecting preproglucagon axons preferentially innervate sympathetic preganglionic neurons

Glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarius (NTS) and medullary reticular formation, produce GLP-1. In transgenic mice expressing glucagon promoter-driven yellow fluorescent protein (YFP), these brainstem PPG neurons project to many central autonomic regions where GLP-1 receptors are expressed. The spinal cord also contains GLP-1 receptor mRNA but the distribution of spinal PPG axons is unknown. Here, we used two-color immunoperoxidase labeling to examine PPG innervation of spinal segments T1–S4 in YFP-PPG mice. Immunoreactivity for YFP identified spinal PPG axons and perikarya. We classified spinal neurons receiving PPG input by immunoreactivity for choline acetyltransferase (ChAT), nitric oxide synthase (NOS) and/or Fluorogold (FG) retrogradely transported from the peritoneal cavity. FG microinjected at T9 defined cell bodies that supplied spinal PPG innervation. The deep dorsal horn of lower lumbar cord contained YFP-immunoreactive neurons. Non-varicose, YFP-immunoreactive axons were prominent in the lateral funiculus, ventral white commissure and around the ventral median fissure. In T1–L2, varicose, YFP-containing axons closely apposed many ChAT-immunoreactive sympathetic preganglionic neurons (SPN) in the intermediolateral cell column (IML) and dorsal lamina X. In the sacral parasympathetic nucleus, about 10% of ChAT-immunoreactive preganglionic neurons received YFP appositions, as did occasional ChAT-positive motor neurons throughout the rostrocaudal extent of the ventral horn. YFP appositions also occurred on NOS-immunoreactive spinal interneurons and on spinal YFP-immunoreactive neurons. Injecting FG at T9 retrogradely labeled many YFP-PPG cell bodies in the medulla but none of the spinal YFP-immunoreactive neurons. These results show that brainstem PPG neurons innervate spinal autonomic and somatic motor neurons. The distributions of spinal PPG axons and spinal GLP-1 receptors correlate well. SPN receive the densest PPG innervation. Brainstem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to SPN or interneurons

Antimicrobial resistance and antimicrobial use animal monitoring policies in Europe: Where are we?

The World Health Organization has recognized antimicrobial resistance as one of the top three threats to human health. Any use of antibiotics in animals will ultimately affect humans and vice versa. Appropriate monitoring of antimicrobial use and resistance has been repeatedly emphasized along with the need for global policies. Under the auspices of the European Union research project, EFFORT, we mapped antimicrobial use and resistance monitoring programs in ten European countries. We then compared international and European guidelines and policies. In resistance monitoring, we did not find important differences between countries. Current resistance monitoring systems are focused on food animal species (using fecal samples). They ignore companion animals. The scenario is different for monitoring antibiotics use. Recently, countries have tried to harmonize methodologies, but reporting of antimicrobial use remains voluntary. We therefore identified a need for stronger policies

Variation between countries in the frequency of diabetic ketoacidosis at first presentation of type 1 diabetes in children: a systematic review.

AIMS/HYPOTHESIS: Type 1 diabetes is the most frequent endocrine disease in children, with 65,000 children diagnosed worldwide every year. Up to 80% of these children present with diabetic ketoacidosis (DKA), which is associated with both short-term risks and long-term consequences. This study aimed to characterise the worldwide variation in presentation of type 1 diabetes to inform future interventions to reduce this excess morbidity and mortality. METHODS: This was a systematic review of studies indexed on PubMed, EMBASE, Web of Science, Scopus or CINAHL before March 2011 that included unselected groups of children presenting with new-onset type 1 diabetes, reported the proportion presenting with DKA and used a definition of DKA based on measurement of pH or bicarbonate. RESULTS: Sixty-five studies of cohorts comprising over 29,000 children in 31 countries were included. The frequency of DKA at diagnosis ranged from 12.8% to 80%, with highest frequencies in the United Arab Emirates, Saudi Arabia and Romania, and the lowest in Sweden, the Slovak Republic and Canada. Multivariable modelling showed the frequency of DKA was inversely associated with gross domestic product, latitude and background incidence of type 1 diabetes. CONCLUSIONS/INTERPRETATION: This is the first description of the variation in frequency of DKA at presentation of type 1 diabetes in children across countries. It demonstrates large variations that may, at least in part, be explained by different levels of disease awareness and healthcare provision and suggests ways to decrease the excess morbidity and mortality associated with DKA at diagnosis

Acceptability of the Cytosponge procedure for detecting Barrett’s oesophagus: A qualitative study

Objective: To investigate the acceptability of the Cytosponge, a novel sampling device to detect Barrett's oesophagus (BE), a precursor to oesophageal adenocarcinoma (EAC), among people with risk factors for this condition. Design: A qualitative study using semistructured interviews and focus group discussions. Data were explored by three researchers using thematic analysis. Setting: Community setting in London, UK. Participants: A recruitment company identified 33 adults (17 men, 16 women) aged 50–69 years with gastro-oesophageal reflux disease (GERD), a risk factor for BE. The majority of participants were white British (73%). The focus groups were stratified by gender and education. 10 individuals were interviewed and 23 participated in four focus groups. Results: 3 key themes emerged from the data: the anticipated physical experience, preferences for the content of information materials and comparisons with the current gold-standard test. Overall acceptability was high, but there was initial concern about the physical experience of taking the test, including swallowing and extracting the Cytosponge. These worries were reduced after handling the device and a video demonstration of the procedure. Knowledge of the relationship between GERD, BE and EAC was poor, and some suggested they would prefer not to know about the link when being offered the Cytosponge. Participants perceived the Cytosponge to be more comfortable, practical and economical than endoscopy. Conclusions: These qualitative data suggest the Cytosponge was acceptable to the majority of participants with risk factors for BE, and could be used as a first-line test to investigate GERD symptoms. Concerns about the physical experience of the test were alleviated through multimedia resources. The development of patient information materials is an important next step to ensuring patients are adequately informed and reassured about the procedure. Patient stakeholders should be involved in this process to ensure their concerns and preferences are considered

Electron gyroscale fluctuation measurements in National Spherical Torus Experiment H-mode plasmas

A collective scattering system has measured electron gyroscale fluctuations in National Spherical Torus Experiment [M. Ono et al., Nucl. Fusion 40, 557 (2000)] H-mode plasmas to investigate electron temperature gradient (ETG) turbulence. Observations and results pertaining to fluctuation measurements in ETG-stable regimes, the toroidal field scaling of fluctuation amplitudes, the relation between fluctuation amplitudes and transport quantities, and fluctuation magnitudes and k-spectra are presented. Collectively, the measurements provide insight and guidance for understanding ETG turbulence and anomalous electron thermal transport. (C) 2009 American Institute of Physics. [doi:10.1063/1.3262530]X116sciescopu

Risk prediction tools for cancer in primary care.

This is the final version of the article. Available from the publisher via the DOI in this record.Numerous risk tools are now available, which predict either current or future risk of a cancer diagnosis. In theory, these tools have the potential to improve patient outcomes through enhancing the consistency and quality of clinical decision-making, facilitating equitable and cost-effective distribution of finite resources such as screening tests or preventive interventions, and encouraging behaviour change. These potential uses have been recognised by the National Cancer Institute as an 'area of extraordinary opportunity' and an increasing number of risk prediction models continue to be developed. The data on predictive utility (discrimination and calibration) of these models suggest that some have potential for clinical application; however, the focus on implementation and impact is much more recent and there remains considerable uncertainty about their clinical utility and how to implement them in order to maximise benefits and minimise harms such as over-medicalisation, anxiety and false reassurance. If the potential benefits of risk prediction models are to be realised in clinical practice, further validation of the underlying risk models and research to assess the acceptability, clinical impact and economic implications of incorporating them in practice are needed

Observations of Reduced Electron Gyroscale Fluctuations in National Spherical Torus Experiment H-Mode Plasmas with Large E X B Flow Shear

Electron gyroscale fluctuation measurements in National Spherical Torus Experiment H-mode plasmas with large toroidal rotation reveal fluctuations consistent with electron temperature gradient (ETG) turbulence. Large toroidal rotation in National Spherical Torus Experiment plasmas with neutral beam injection generates ExB flow shear rates comparable to ETG linear growth rates. Enhanced fluctuations occur when the electron temperature gradient is marginally stable with respect to the ETG linear critical gradient. Fluctuation amplitudes decrease when the ExB flow shear rate exceeds ETG linear growth rates. The observations indicate that ExB flow shear can be an effective suppression mechanism for ETG turbulence.X1129sciescopu

Internal transport barriers in the National Spherical Torus Experiment

In the National Spherical Torus Experiment [M. Ono , Nucl. Fusion 41, 1435 (2001)], internal transport barriers (ITBs) are observed in reversed (negative) shear discharges where diffusivities for electron and ion thermal channels and momentum are reduced. While neutral beam heating can produce ITBs in both electron and ion channels, high harmonic fast wave heating can also produce electron ITBs (e-ITBs) under reversed magnetic shear conditions without momentum input. Interestingly, the location of the e-ITB does not necessarily match that of the ion ITB (i-ITB). The e-ITB location correlates best with the magnetic shear minima location determined by motional Stark effect constrained equilibria, whereas the i-ITB location better correlates with the location of maximum ExB shearing rate. Measured electron temperature gradients in the e-ITB can exceed critical gradients for the onset of electron thermal gradient microinstabilities calculated by linear gyrokinetic codes. A high-k microwave scattering diagnostic shows locally reduced density fluctuations at wave numbers characteristic of electron turbulence for discharges with strongly negative magnetic shear versus weakly negative or positive magnetic shear. Reductions in fluctuation amplitude are found to be correlated with the local value of magnetic shear. These results are consistent with nonlinear gyrokinetic simulations predicting a reduction in electron turbulence under negative magnetic shear conditions despite exceeding critical gradients.X1128sciescopu

Global change synergies and trade-offs between renewable energy and biodiversity

Reliance on fossil fuels is causing unprecedented climate change and is accelerating environmental degradation and global biodiversity loss. Together, climate change and biodiversity loss, if not averted urgently, may inflict severe damage on ecosystem processes, functions and services that support the welfare of modern societies. Increasing renewable energy deployment and expanding the current protected area network represent key solutions to these challenges, but conflicts may arise over the use of limited land for energy production as opposed to biodiversity conservation. Here, we compare recently identified core areas for the expansion of the global protected area network with the renewable energy potential available from land-based solar photovoltaic, wind energy and bioenergy (in the form of Miscanthus 9 giganteus). We show that these energy sources have very different biodiversity impacts and net energy contributions. The extent of risks and opportunities deriving from renewable energy development is highly dependent on the type of renewable source harvested, the restrictions imposed on energy harvest and the region considered, with Central America appearing at particularly high potential risk from renewable energy expansion. Without restrictions on power generation due to factors such as production and transport costs, we show that bioenergy production is a major potential threat to biodiversity, while the potential impact of wind and solar appears smaller than that of bioenergy. However, these differences become reduced when energy potential is restricted by external factors including local energy demand. Overall, we found that areas of opportunity for developing solar and wind energy with little harm to biodiversity could exist in several regions of the world, with the magnitude of potential impact being particularly dependent on restrictions imposed by local energy demand. The evidence provided here helps guide sustainable development of renewable energy and contributes to the targeting of global efforts in climate mitigation and biodiversity conservation

Risk prediction models for colorectal cancer in people with symptoms: a systematic review.

Colorectal cancer (CRC) is the fourth leading cause of cancer-related death in Europe and the United States. Detecting the disease at an early stage improves outcomes. Risk prediction models which combine multiple risk factors and symptoms have the potential to improve timely diagnosis. The aim of this review is to systematically identify and compare the performance of models that predict the risk of primary CRC among symptomatic individuals. We searched Medline and EMBASE to identify primary research studies reporting, validating or assessing the impact of models. For inclusion, models needed to assess a combination of risk factors that included symptoms, present data on model performance, and be applicable to the general population. Screening of studies for inclusion and data extraction were completed independently by at least two researchers. Twelve thousand eight hundred eight papers were identified from the literature search and three through citation searching. 18 papers describing 15 risk models were included. Nine were developed in primary care populations and six in secondary care. Four had good discrimination (AUROC > 0.8) in external validation studies, and sensitivity and specificity ranged from 0.25 and 0.99 to 0.99 and 0.46 depending on the cut-off chosen. Models with good discrimination have been developed in both primary and secondary care populations. Most contain variables that are easily obtainable in a single consultation, but further research is needed to assess clinical utility before they are incorporated into practice.JUS is funded by a National Institute of Health Research (NIHR) Clinica