Single-frequency violet and blue laser emission from AlGaInN photonic integrated circuit chips.

Chip-based, single-frequency and low phase-noise integrated photonic laser diodes emitting in the violet (412 nm) and blue (461 nm) regime are demonstrated. The GaN-based edge-emitting laser diodes were coupled to high-quality on-chip micro-resonators for optical feedback and mode selection resulting in laser self-injection locking with narrow emission linewidth. Multiple group III-nitride (III-N) based photonic integrated circuit chips with different waveguide designs including single-crystalline AlN, AlGaN, and GaN were developed and characterized. Single-frequency laser operation was demonstrated for all studied waveguide core materials. The best side-mode suppression ratio was determined to be ∼36 dB at 412 nm with a single-frequency laser emission linewidth of only 3.8 MHz at 461 nm. The performance metrics of this novel, to the best of our knowledge, type of laser suggest potential implementation in next-generation, portable quantum systems.

Nanoscale real-time detection of quantum vortices at millikelvin temperatures.

Since we still lack a theory of classical turbulence, attention has focused on the conceptually simpler turbulence in quantum fluids. Reaching a better understanding of the quantum case may provide additional insight into the classical counterpart. That said, we have hitherto lacked detectors capable of the real-time, non-invasive probing of the wide range of length scales involved in quantum turbulence. Here we demonstrate the real-time detection of quantum vortices by a nanoscale resonant beam in superfluid 4He at 10 mK. Essentially, we trap a single vortex along the length of a nanobeam and observe the transitions as a vortex is either trapped or released, detected through the shift in the beam resonant frequency. By exciting a tuning fork, we control the ambient vortex density and follow its influence on the vortex capture and release rates demonstrating that these devices are capable of probing turbulence on the micron scale.

Sources, variability and parameterizations of intra-city factors obtained from dispersion-normalized multi-time resolution factor analyses of PM2.5 in an urban environment.

Ambient fine particulate matter (PM2.5) data of similar continuously monitored species at two air monitoring sites with different characteristics within the City of Toronto were used to gauge the intra-city variations in the PM composition over a largely concurrent period spanning two years. One location was <8 m from the side of a major highway while the other was an urban background location. For the first time, multi-time resolution factor analysis was applied to dispersion-normalized concentrations to identify and quantify source contributions while reducing the influence of local meteorology. These factors were particulate sulphate (pSO4), particulate nitrate (pNO3), secondary organic aerosols (SOA), crustal matter (CrM) that were common to both sites, a hydrocarbon-like organic matter (HOM) exclusive to the urban background site, three black carbon related factors (BC, BC-HOM at the highway site, and a brown carbon rich factor (BC-BrC) at the urban background site), biomass burning organic matter (BBOM) and brake dust (BD) factors exclusive to the highway site. The PM2.5 composition was different between these two locations, over only a 10 km distance. The sum of SOA, pSO4 and pNO3 at the urban background site averaged 57% of the PM2.5 mass while the same species represented 43% of the average PM2.5 mass at the highway site. Local or site-specific factors may be of greater interest for control policy design. Thus, regression analyses with potential explanatory, site-specific variables were performed for results from the highway site. Three model approaches were explored: multiple linear regression (MLR), regression with a generalized reduced gradient (GRG) algorithm, and a generalized additive model (GAM). GAM gave the largest fraction of variance for the locally-found factors at the highway site. Heavy-duty vehicles were most important for explaining the black carbon (BC and BC-HOM) factors. Light-duty vehicles were dominant for the brake dust (BD) factor. The auxiliary modelling for the local factors showed that the traffic-related factors likely originated along the main roadways at their respective sites while the more regional factors, - pSO4, pNO3, SOA, - had sources that were both regional and local in origin and with contributions that varied seasonally. These results will be useful in understanding ambient particulate matter sources on a city scale that will support air quality management planning.

Acute myocardial injury after administration of intravenous epinephrine for allergic reaction.

Myocardial injury or infarction in the setting of anaphylaxis can be due to anaphylaxis itself, known as Kounis syndrome, or as a result of treatment with epinephrine. Myocardial ischemia caused by therapeutic doses of epinephrine in the setting of anaphylaxis is a rare event attributed to coronary artery vasospasm. A 41-year-old female with past medical history of recurrent costochondritis, chronic thrombocytopenia, and nonspecific palindromic rheumatism presented to the emergency department with perioral numbness, flushing and throat tightness after a meal containing fish and almonds. Intramuscular epinephrine was ordered but inadvertently administered intravenously, after which she developed sharp, substernal chest pain and palpitations. Electrocardiogram showed normal sinus rhythm with QT interval prolongation. Troponin peaked at 1.41 ng/mL. She was given 324 mg of aspirin in the emergency department. Transthoracic echocardiogram showed normal ejection fraction with lateral wall motion abnormality. We present a case of a patient with no significant risk factors for coronary artery disease who developed myocardial injury following inadvertent IV administration of a therapeutic dose of epinephrine for an anaphylactic-like reaction. The development of myocardial injury after epinephrine is rare, with only six reported cases in literature and just one after intravenous administration. This is the first described case of known myocardial injury without ST-T wave changes on electrocardiogram . The proposed mechanism is an alpha-1 receptor-mediated coronary vascular spasm resulting in myocardial ischemia. The aim of this case is to raise awareness of the potential for acute myocardial injury after inadvertent intravenous administration of epinephrine for anaphylaxis, even in patients with no known risk factors for coronary artery disease, as well as to demonstrate that this clinical scenario can present regardless of troponin elevation and without ST-T wave ECG changes.

Turing Instability in the Solid State: Void Lattices in Irradiated Metals.

Turing (or double-diffusive) instabilities describe pattern formation in reaction-diffusion systems, and were proposed in 1952 as a potential mechanism behind pattern formation in nature, such as leopard spots and zebra stripes. Because the mechanism requires the reacting species to have significantly different diffusion rates, only a few liquid phase chemical reaction systems exhibiting the phenomenon have been discovered. In solids the situation is markedly different, since species such as impurities or other defects typically have mobilities ∝exp(-E/k_{B}T), where E is the migration barrier and T is the temperature. This often leads to mobilities differing by several orders of magnitude. Here, we use a simple, minimal model to show that an important class of emergent patterns in solids, namely void superlattices in irradiated metals, could also be explained by the Turing mechanism. Analytical results are confirmed by phase field simulations. The model (Cahn-Hilliard equations for interstitial and vacancy concentrations, coupled by generation and annihilation terms) is generic, and the mechanism could also be responsible for the patterns and structure observed in many solid state systems.

LEGO® Block Structures as a Sub-Kelvin Thermal Insulator.

We report measurements of the thermal conductance of a structure made from commercial Acrylonitrile Butadiene Styrene (ABS) modules, known as LEGO® blocks, in the temperature range from 70 mK to 1.8 K. A power law for the sample's thermal conductivity κ = (8.7 ± 0.3) × 10-5 T 1.75±0.02 WK-1 m-1 was determined. We conclude that this ABS/void compound material provides better thermal isolation than well-known bulk insulator materials in the explored temperature range, whilst maintaining solid support. LEGO blocks represent a cheap and superlative alternative to materials such as Macor or Vespel. In our setup, <400 nW of power can heat an experimental area of 5 cm2 to over 1 K, without any significant change to the base temperature of the dilution refrigerator. This work suggests that custom-built modular materials with even better thermal performance could be readily and cheaply produced by 3D printing.

Operating Nanobeams in a Quantum Fluid.

Microelectromechanical (MEMS) and nanoelectromechanical systems (NEMS) are ideal candidates for exploring quantum fluids, since they can be manufactured reproducibly, cover the frequency range from hundreds of kilohertz up to gigahertz and usually have very low power dissipation. Their small size offers the possibility of probing the superfluid on scales comparable to, and below, the coherence length. That said, there have been hitherto no successful measurements of NEMS resonators in the liquid phases of helium. Here we report the operation of doubly-clamped aluminium nanobeams in superfluid 4He at temperatures spanning the superfluid transition. The devices are shown to be very sensitive detectors of the superfluid density and the normal fluid damping. However, a further and very important outcome of this work is the knowledge that now we have demonstrated that these devices can be successfully operated in superfluid 4He, it is straightforward to apply them in superfluid 3He which can be routinely cooled to below 100 µK. This brings us into the regime where nanomechanical devices operating at a few MHz frequencies may enter their mechanical quantum ground state.

Promoting health and reducing costs: a role for reform of self-monitoring of blood glucose provision within the National Health Service.

AIM: To determine the cost-effectiveness of all options for the self-monitoring of blood glucose funded by the National Health Service, providing guidance for disinvestment and testing the hypothesis that advanced meter features may justify higher prices. METHODS: Using data from the Health and Social Care Information Centre concerning all 8 340 700 self-monitoring of blood glucose-related prescriptions during 2013/2014, we conducted a cost-minimization analysis, considering both strip and lancet costs, including all clinically equivalent technologies for self-monitoring of blood glucose, as determined by the ability to meet ISO-15197:2013 guidelines for meter accuracy. RESULTS: A total of 56 glucose monitor, test strip and lancet combinations were identified, of which 38 met the required accuracy standards. Of these, the mean (range) net ingredient costs for test strips and lancets were £0.27 (£0.14-£0.32) and £0.04 (£0.02-£0.05), respectively, resulting in a weighted average of £0.28 (£0.18-£0.37) per test. Systems providing four or more advanced features were priced equal to those providing just one feature. A total of £12 m was invested in providing 42 million self-monitoring of blood glucose tests with systems that fail to meet acceptable accuracy standards, and efficiency savings of £23.2 m per annum are achievable if the National Health Service were to disinvest from technologies providing lesser functionality than available alternatives, but at a much higher price. CONCLUSION: The study uncovered considerable variation in the price paid by the National Health Service for self-monitoring of blood glucose, which could not be explained by the availability of advanced meter features. A standardized approach to self-monitoring of blood glucose prescribing could achieve significant efficiency savings for the National Health Service, whilst increasing overall utilisation and improving safety for those currently using systems that fail to meet acceptable standards for measurement accuracy.

cFLIP is critical for oligodendrocyte protection from inflammation.

Neuroinflammation associated with degenerative central nervous system disease and injury frequently results in oligodendrocyte death. While promoting oligodendrocyte viability is a major therapeutic goal, little is known about protective signaling strategies. We report that in highly purified rat oligodendrocytes, interferon gamma (IFNγ) activates a signaling pathway that protects these cells from tumor necrosis factor alpha (TNFα)-induced cytotoxicity. IFNγ protection requires Jak (Janus kinase) activation, components of the integrated stress response and NF-κB activation. Although NF-κB activation also occurred transiently in the absence of IFNγ and presence of TNFα, this activation was not sufficient to prevent induction of the TNFα-responsive cell death pathway. Genetic inhibition of NF-κB translocation to the nucleus abrogated IFNγ-mediated protection and did not change the cell death induced by TNFα, suggesting that NF-κB activation via IFNγ induces a different set of responses than activation of NF-κB via TNFα. A promising candidate is the NF-κB target cFLIP (cellular FLICE (FADD-like IL-1ß-converting enzyme)-inhibitory protein), which is protease-deficient caspase homolog that inhibits caspase-3 activation. We show that IFNγ-mediated protection led to upregulation of cFLIP. Overexpression of cFLIP was sufficient for oligodendrocyte protection from TNFα and short hairpin RNA knockdown of cFLIP-abrogated IFNγ -mediated protection. To determine the relevance of our in vitro finding to the more complex in vivo situation, we determined the impact on oligodendrocyte death of regional cFLIP loss of function in a murine model of neuroinflammation. Our data show that downregulation of cFLIP during inflammation leads to death of oligodendrocytes and decrease of myelin in vivo. Taken together, we show that IFNγ-mediated induction of cFLIP expression provides a new mechanism by which this cytokine can protect oligodendrocytes from TNFα-induced cell death.

Immediate direct peripheral vasoconstriction in response to hyperinsulinemia and metformin in the anesthetized pig.

Elevated levels of insulin have been reported to induce both an arterial vasodilation mediated by nitric oxide (NO), and vasoconstriction mediated by endothelin and reactive oxygen radicals. Metformin, used to control blood glucose levels in type 2 diabetes, has also been shown to cause NO-mediated dilation of conduit arteries. It is possible that these contradictory vascular effects are due to a non-direct action on arteries. Therefore, the direct effect of high levels of insulin and metformin infusion on resistance artery diameter was evaluated. Experiments were carried out on the anesthetized pig; blood flow and pressure were measured in the iliac artery. An adjustable snare was applied to the iliac above the pressure and flow measurement site to induce step decreases (3-4 occlusions at 5 min intervals were performed for each infusion) in blood flow, and hence iliac pressure, and the conductance (deltaflow / deltapressure) calculated. Saline, insulin (20 and 40 mUSP/l/min), and metformin (1 microg/ml/min) were infused separately downstream of the adjustable snare and their effect on arterial conductance assessed. Insulin at both infusion rates and metformin caused a significant reduction in peripheral vascular conductance. In conclusion, hyperinsulinemia and metformin infusion constrict resistance arterial vessels in vivo.

Responses of iliac conduit artery and hindlimb resistance vessels to luminal hyperfructosemia in the anaesthetized pig.

AIMS: High fructose levels are found in diabetes mellitus, associated with high corn syrup diets, and have been claimed to cause hypertension. As the direct effects on conduit and resistance arteries have not been previously reported, we measured these in vivo in the anaesthetized pig with instrumented iliac arteries. METHODS: Experiments were performed on the iliac artery preparation in the anaesthetized pig: blood flow, diameter and pressure were measured in the iliac. RESULTS: The change in diameter of an occluded iliac artery segment filled with hyperfructosemic (15 µm) blood was 89.5 ± 22.1 µm (mean ± SE), contrasted with 7.7 ± 13.06 µm control (P = 0.005, paired t-test, n = 6). There was no significant difference when compared with blood containing both hyperfructosemic blood and the nitric oxide synthesis inhibitor, N(G)-nitro-l-arginine methyl ester (250 µg mL(-1)). Step changes in pressure and flow were achieved by progressive arterial stenosis during control saline and 15 µm min(-1) fructose downstream intra-arterial infusions. Linear regression of the step changes in blood pressure versus the instantaneous step changes in blood flow showed a statistically significant decrease in slope of the conductance (P < 0.001, analysis of covariance), indicating an increase in instantaneous peripheral vascular resistance. Peripheral autoregulation and conduit artery shear-stress-mediated dilatation were not significantly altered. CONCLUSION: An elevated level of fructose caused dilatation of a conduit artery but constriction of resistance vessels. The latter effect could account, if maintained long-term, for the hypertension claimed to be due to hyperfuctosemia.

Making health care safer II: an updated critical analysis of the evidence for patient safety practices.

OBJECTIVES: To review important patient safety practices for evidence of effectiveness, implementation, and adoption. DATA SOURCES: Searches of multiple computerized databases, gray literature, and the judgments of a 20-member panel of patient safety stakeholders. REVIEW METHODS: The judgments of the stakeholders were used to prioritize patient safety practices for review, and to select which practices received in-depth reviews and which received brief reviews. In-depth reviews consisted of a formal literature search, usually of multiple databases, and included gray literature, where applicable. In-depth reviews assessed practices on the following domains: • How important is the problem? • What is the patient safety practice? • Why should this practice work? • What are the beneficial effects of the practice? • What are the harms of the practice? • How has the practice been implemented, and in what contexts? • Are there any data about costs? • Are there data about the effect of context on effectiveness? We assessed individual studies for risk of bias using tools appropriate to specific study designs. We assessed the strength of evidence of effectiveness using a system developed for this project. Brief reviews had focused literature searches for focused questions. All practices were then summarized on the following domains: scope of the problem, strength of evidence for effectiveness, evidence on potential for harmful unintended consequences, estimate of costs, how much is known about implementation and how difficult the practice is to implement. Stakeholder judgment was then used to identify practices that were "strongly encouraged" for adoption, and those practices that were "encouraged" for adoption. RESULTS: From an initial list of over 100 patient safety practices, the stakeholders identified 41 practices as a priority for this review: 18 in-depth reviews and 23 brief reviews. Of these, 20 practices had their strength of evidence of effectiveness rated as at least "moderate," and 25 practices had at least "moderate" evidence of how to implement them. Ten practices were classified by the stakeholders as having sufficient evidence of effectiveness and implementation and should be "strongly encouraged" for adoption, and an additional 12 practices were classified as those that should be "encouraged" for adoption. CONCLUSIONS: The evidence supporting the effectiveness of many patient safety practices has improved substantially over the past decade. Evidence about implementation and context has also improved, but continues to lag behind evidence of effectiveness. Twenty-two patient safety practices are sufficiently well understood, and health care providers can consider adopting them now.

Time encoded multicolor fluorescence detection in a microfluidic flow cytometer.

We describe an optical detection technique that delivers high signal-to-noise discrimination to enable a multi-parameter flow cytometer that combines high performance, robustness, compactness and low cost. The enabling technique is termed "spatially modulated detection" and generates a time-dependent signal as a continuously fluorescing (bio-) particle traverses an optical transmission pattern along the fluidic channel. Correlating the detected signal with the expected transmission pattern achieves high discrimination of the particle signal from background noise. Additionally, the particle speed and its fluorescence emission characteristics are deduced from the correlation analysis. Our method uses a large excitation/emission volume along the fluidic channel in order to increase the total flux of fluorescence light that originates from a particle while requiring minimal optical alignment. Despite the large excitation/detection volume, the mask pattern enables a high spatial resolution in the micron range. This allows for detection and characterization of particles with a separation (in flow direction) comparable to the dimension of individual particles. In addition, the concept is intrinsically tolerant of non-encoded background fluorescence originating from fluorescent components in solution, fluorescing components of the chamber and contaminants on its surface. The optical detection technique is illustrated with experimental results of multicolor detection with a single large area detector by filtering fluorescence emission of different particles through a patterned color mask. Thereby the particles' fluorescence emission spectrum is encoded in a time dependent intensity signal and color information can be extracted from the correlation analysis. The multicolor detection technique is demonstrated by differentiation of micro-beads loaded with PE (Phycoerythrin) and PE-Cy5 that are excited at 532 nm.

Update on the important new drug target in cardiovascular medicine - the vascular glycocalyx.

We reviewed this subject in 2009, pointing out that, to the process of atherothrombosis, glycocalyx dysfunction and damage must be added to the previous known causitive factors. Glycocalyx dysfunction is possibly the very first step in the process of atherothrombosis, being a protective layer between the endothelial cells and the blood. We emphasise the unique feature of glycocalyx mediated vasodilatation in that it is initiated purely by mechanical changes, i.e., changes in vascular wall shear stress, allowing conduit arteries to adjust diameter to demanded blood flow rate. The predeliction of atheroma to sites of low shear stress, the inhibition of the shear response by lumenal hyperglycaemia, and the fact that the response is mediated by nitric oxide (NO), an anti-atheromatous agent has led to the hypothesis that impairment of this pathway is pro-atherogenic. In the microcirculation it has been shown that the glycocalyx must be added to the factors involved in the Starling hypothesis of tissue fluid generation and exchange. As a consequence glycoalyx dysfunction in hyperglycaemia has been postulated to cause oedema and microalbinuria. We suggested that perhaps the arterial glycocalyx will become the most important for future early prevention of people at risk of cardiovascular disease. The advances in this subject since 2009 are the subject of the present review. What has struck us when searching the literature is that research into the glycocalyx has increased very much and now comes from many disciplines; e.g., diabetes, hypertension, bioengineering, physiology, critical care, cardiology, shock. This update is by no means exhaustive, but hopes, again, to bring to the attention of the pharmaceutical industry, the need for grants in the appropriate experimental models.

Dependence of smooth muscle tone upon pulsatility in the iliac artery of the anaesthetised pig.

The aim of the study was to examine features of the myogenic response of a conduit artery to the presence and absence of pulsatile pressure. The iliac arteries of 16 anaesthetised pigs (10 in control conditions, 6 under sympathetic blockade) were instrumented with flowmeter, sonomicrometry crystals for diameter measurement, a micro-tip manometer for pressure measurement and snares placed proximally and distally to the crystals to isolate a test segment from the remainder of the arterial system. When the snares were tightened to occlude the test segment, systemic arterial pressure remained constant. There was a large shift in the pressure-diameter relationship, in that there was a rapid decline in test segment pressure for the same diameter. This indicated arterial wall smooth muscle relaxation in response to removal of pulsatility of arterial pressure. The difference in mean pressure between pulsatility present and absent was significant (p < 0.0001, paired t test, n = 10). Before proximal and distal occlusion, test segment pressure was (mean ± SD) 92.26 ± 12.39 mmHg, whereas after distal and proximal occlusion at the same diameter, it was 42.34 ± 10.87 mmHg. We conclude that in the presence of pulsatile pressure, there is a large proportion of arterial wall smooth muscle tone related to stretch of the arterial wall during the cardiac cycle, indicating that, under normal pulsatile pressure conditions, much of the normal tone can be attributed to the pulsatile component of the arterial myogenic response.

Presenting your structures: the CCP4mg molecular-graphics software.

CCP4mg is a molecular-graphics program that is designed to give rapid access to both straightforward and complex static and dynamic representations of macromolecular structures. It has recently been updated with a new interface that provides more sophisticated atom-selection options and a wizard to facilitate the generation of complex scenes. These scenes may contain a mixture of coordinate-derived and abstract graphical objects, including text objects, arbitrary vectors, geometric objects and imported images, which can enhance a picture and eliminate the need for subsequent editing. Scene descriptions can be saved to file and transferred to other molecules. Here, the substantially enhanced version 2 of the program, with a new underlying GUI toolkit, is described. A built-in rendering module produces publication-quality images.

Burden of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay associated with bloodstream infections due to Escherichia coli resistant to third-generation cephalosporins.

OBJECTIVES: This study determined excess mortality and length of hospital stay (LOS) attributable to bloodstream infection (BSI) caused by third-generation-cephalosporin-resistant Escherichia coli in Europe. METHODS: A prospective parallel matched cohort design was used. Cohort I consisted of patients with third-generation-cephalosporin-resistant E. coli BSI (REC) and cohort II consisted of patients with third-generation-cephalosporin-susceptible E. coli BSI (SEC). Patients in both cohorts were matched for LOS before infection with patients free of the respective BSI. Thirteen European tertiary care centres participated between July 2007 and June 2008. RESULTS: Cohort I consisted of 111 REC patients and 204 controls and cohort II consisted of 1110 SEC patients and 2084 controls. REC patients had a higher mortality at 30 days (adjusted odds ratio = 4.6) and a higher hospital mortality (adjusted hazard ratio = 5.7) than their controls. LOS was increased by 8 days. For SEC patients, these figures were adjusted odds ratio = 1.9, adjusted hazard ratio = 2.0 and excess LOS = 3 days. A 2.5 times [95% confidence interval (95% CI) 0.9-6.8] increase in all-cause mortality at 30 days and a 2.9 times (95% CI 1.2-6.9) increase in mortality during entire hospital stay as well as an excess LOS of 5 days (95% CI 0.4-10.2) could be attributed to resistance to third-generation cephalosporins in E. coli BSI. CONCLUSIONS: Morbidity and mortality attributable to third-generation-cephalosporin-resistant E. coli BSI is significant. If prevailing resistance trends continue, high societal and economic costs can be expected. Better management of infections caused by resistant E. coli is becoming essential.