Guidelines for type 2 diabetes: keeping a finger on the pulse

Cardiovascular disease remains the biggest cause of morbidity and mortality in patients with type 2 diabetes.1 Individual drugs from two classes of glucose-lowering agents, glucagon-like peptide-1 (GLP-1)receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors, have been shown in recent clinical trials to improve cardiovascular outcomes in patients with type 2 diabetes at high risk of cardiovascular disease. These new data are reflected in guidelines from several professional associations, but not in the National Institute for Health and Care Excellence (NICE) guidelines in the UK.2 We believe that NICE and other national and international health authorities should respond rapidly to new data, particularly when there is potential to improve outcomes and save lives

CO2 Transport Systems Development: Status of Three Large European CCS Demonstration Projects with EEPR Funding

AbstractThis paper addresses technical and operational aspects pertaining to the transport of CO2. It deals with lessons learnt from the development of three large CCS demonstration projects: the UK-based Don Valley project, the Dutch ROAD project, and the Spanish Compostilla project. These projects were all selected by the European Commission in 2009 to receive funding under the European Energy Programme for Recovery (EEPR). The purpose of the demonstration projects is to verify feasible capture techniques (i.e. gasification, flue-gas cleaning, and oxy-coal combustion in circulating fluidised bed, respectively), and to demonstrate geological storage options, off-shore and on-shore. As the distance and elevation of the CO2 transport system are inherently given by the project, the transport conditions for the CO2 will generally differ from one project to another.The demonstration projects have shown that the thermophysical nature of CO2 is prone to complicate certain operational procedures mainly due to phenomena like phase change, hydrate formation and Joule-Thomson cooling. The front-end engineering design studies suggest, however, that the handling of CO2 is quite feasible during normal operation, although customised solutions may be required to handle transients like emergency shut-down and pipeline re-pressurisation. This implies that CO2 transport is not seen as an insuperable hurdle to the design and operation of large CCS systems

Chemoreception and neuroplasticity in respiratory circuits

The respiratory central pattern generator must respond to chemosensory cues to maintain oxygen (O2) and carbon dioxide (CO2) homeostasis in the blood and tissues. To do this, sensorial cells located in the periphery and central nervous system monitor the arterial partial pressure of O2 and CO2 and initiate respiratory and autonomic reflex adjustments in conditions of hypoxia and hypercapnia. In conditions of chronic intermittent hypoxia (CIH), repeated peripheral chemoreceptor input mediated by the nucleus of the solitary tract induces plastic changes in respiratory circuits that alter baseline respiratory and sympathetic motor outputs and result in chemoreflex sensitization, active expiration, and arterial hypertension. Herein, we explored the hypothesis that the CIH-induced neuroplasticity primarily consists of increased excitability of pre-inspiratory/inspiratory neurons in the pre-Bötzinger complex. To evaluate this hypothesis and elucidate neural mechanisms for the emergence of active expiration and sympathetic overactivity in CIH-treated animals, we extended a previously developed computational model of the brainstem respiratory-sympathetic network to reproduce experimental data on peripheral and central chemoreflexes post-CIH. The model incorporated neuronal connections between the 2nd-order NTS neurons and peripheral chemoreceptors afferents, the respiratory pattern generator, and sympathetic neurons in the rostral ventrolateral medulla in order to capture key features of sympathetic and respiratory responses to peripheral chemoreflex stimulation. Our model identifies the potential neuronal groups recruited during peripheral chemoreflex stimulation that may be required for the development of inspiratory, expiratory and sympathetic reflex responses. Moreover, our model predicts that pre-inspiratory neurons in the pre-Bötzinger complex experience plasticity of channel expression due to excessive excitation during peripheral chemoreflex. Simulations also show that, due to positive interactions between pre-inspiratory neurons in the pre-Bötzinger complex and expiratory neurons in the retrotrapezoid nucleus, increased excitability of the former may lead to the emergence of the active expiratory pattern at normal CO2 levels found after CIH exposure. We conclude that neuronal type specific neuroplasticity in the pre-Bötzinger complex induced by repetitive episodes of peripheral chemoreceptor activation by hypoxia may contribute to the development of sympathetic over-activity and hypertension

Mid infrared near-field fingerprint spectroscopy of the 2D electron gas in LaAlO3_3/SrTiO3_3 at low temperatures

Confined electron systems, such as 2D electron gases (2DEGs), 2D materials, or topological insulators show great technological promise but their susceptibility to defects often results in nanoscale inhomogeneities with unclear origins. Scattering-type scanning near-field optical microscopy (s-SNOM) is useful to investigate buried confined electron systems non-destructively with nanoscale resolution, however, a clear separation of carrier concentration and mobility was often impossible in s-SNOM. Here, we predict a previously inaccessible characteristic "fingerprint" response of the prototypical LaAlO$_3$/SrTiO$_3$ 2DEG, and verify this using a state-of-the-art tunable narrow-band laser in mid-infrared cryo-s-SNOM at 8 K. Our modelling allows us to separate the influence of carrier concentration and mobility on fingerprint spectra and to characterize 2DEG inhomogeneities on the nanoscale. This spatially resolved information about the local electronic properties can be used to identify the origin of inhomogeneities in confined electron systems, making the s-SNOM fingerprint response a valuable tool for nanoelectronics and quantum technology

Challenges and opportunities of achieving European CO₂ transportation and storage specifications for carbon capture in the iron and steel industry

The application of CCS in the iron and steel industry faces particular challenges for achieving European CO2 transportation and storage in meeting CO₂ stream impurity limit specifications due to the unique and diverse composition of the steelworks off-gases targeted for CO₂ capture and the separation efficiency of proposed CO₂ capture solutions. This paper reviews the range and levels of compounds that could form potential CO₂ impurities in steelworks off-gases and provides estimates of the quality of CO₂ products obtained in primary CO₂ capture steps from Blast Furnace Gas (BFG) using different technologies of Pressure-Swing Adsorption (PSA) and amine scrubbing. Published CO₂ specifications from European transportation and storage operators are reviewed and compared. Additional suitable purification steps that are needed in order to reduce the levels of impurities from primary CO₂ product streams in order to achieve European CO₂ impurity limit specifications are identified, characterised and the associated cost implications discussed

Protection From Clinical Peripheral Sensory Neuropathy in Alström Syndrome in Contrast to Early-Onset Type 2 Diabetes

OBJECTIVE—Alström syndrome, with type 2 diabetes, and blindness could confer a high risk of foot ulceration. Clinical testing for neuropathy in Alström syndrome and matched young-onset type 2 diabetic subjects was therefore undertaken

Ensemble reweighting using Cryo-EM particles

Cryo-electron microscopy (cryo-EM) has recently become a premier method for obtaining high-resolution structures of biological macromolecules. However, it is limited to biomolecular samples with low conformational heterogeneity, where all the conformations can be well-sampled at many projection angles. While cryo-EM technically provides single-molecule data for heterogeneous molecules, most existing reconstruction tools cannot extract the full distribution of possible molecular configurations. To overcome these limitations, we build on a prior Bayesian approach and develop an ensemble refinement framework that estimates the ensemble density from a set of cryo-EM particles by reweighting a prior ensemble of conformations, e.g., from molecular dynamics simulations or structure prediction tools. Our work is a general approach to recovering the equilibrium probability density of the biomolecule directly in conformational space from single-molecule data. To validate the framework, we study the extraction of state populations and free energies for a simple toy model and from synthetic cryo-EM images of a simulated protein that explores multiple folded and unfolded conformations