Cardioprotective effects of insulin: how intensive insulin therapy may benefit cardiac surgery patients

Interest in the effects of insulin on the heart came with the recognition that hyperglycemia in the context of myocardial infarction is associated with increased risks of mortality, congestive heart failure, or cardiogenic shock. More recently, instigated by research findings on stress hyperglycemia in critical illness, this interest has been extended to the influence of insulin on clinical outcome after cardiac surgery. Even in nondiabetic individuals, stress hyperglycemia commonly occurs as a key metabolic response to critical illness, eg, after surgical trauma. It is recognized as a major pathophysiological feature of organ dysfunction in the critically ill. The condition stems from insulin resistance brought about by dysregulation of key homeostatic processes, which implicates immune/inflammatory, endocrine, and metabolic pathways. It has been associated with adverse clinical outcomes, including increased mortality, increased duration of mechanical ventilation, increased intensive care unit (ICU) and hospital stay, and increased risk of infection. Hyperglycemia in critical illness is managed with exogenous insulin as standard treatment; however, there is considerable disagreement among experts in the field as to what target blood glucose level is optimal for the critically ill patient. Conventionally, the aim of insulin therapy has been to maintain blood glucose levels below the renal threshold, typically 220 mg/dL (12.2 mmol/L). In recent years, some have advocated tight glycemic control (TGC) with intensive insulin therapy (IIT) to normalize blood glucose levels to within the euglycemic range, typically 80 to 110 mg/dL (4.4–6.1 mmol/L).

Using meteorological wind data to estimate turbine generation output: a sensitivity analysis

Various studies investigating the future impacts of integrating high levels of renewable energy make use of historical meteorological (met) station data to produce estimates of future generation. Hourly means of 10m horizontal wind are extrapolated to a standard turbine hub height using the wind profile power or log law and used to simulate the hypothetical power output of a turbine at that location; repeating this procedure using many viable locations can produce a picture of future electricity generation. However, the estimate of hub height wind speed is dependent on the choice of the wind shear exponent a or the roughness length z0, and requires a number of simplifying assumptions. This paper investigates the sensitivity of this estimation on generation output using a case study of a met station in West Freugh, Scotland. The results show that the choice of wind shear exponent is a particularly sensitive parameter which can lead to significant variation of estimated hub height wind speed and hence estimated future generation potential of a region.

A study into the accuracy of using meteorological wind data to estimate turbine generation output

Meteorological (met) station data is used as the basis for a number of influential studies into the impacts of the variability of renewable resources. Real turbine output data is not often easy to acquire, whereas meteorological wind data, supplied at a standardised height of 10 m, is widely available. This data can be extrapolated to a standard turbine height using the wind profile power law and used to simulate the hypothetical power output of a turbine. Utilising a number of met sites in such a manner can develop a model of future wind generation output. However, the accuracy of this extrapolation is strongly dependent on the choice of the wind shear exponent alpha. This paper investigates the accuracy of the simulated generation output compared to reality using a wind farm in North Rhins, Scotland and a nearby met station in West Freugh. The results show that while a single annual average value for alpha may be selected to accurately represent the long term energy generation from a simulated wind farm, there are significant differences between simulation and reality on an hourly power generation basis, with implications for understanding the impact of variability of renewables on short timescales, particularly system balancing and the way that conventional generation may be asked to respond to a high level of variable renewable generation on the grid in the future.

Carbon monoxide induces cardiac arrhythmia via induction of the late Na+ current

Our data indicate that the proarrhythmic effects of CO arise from activation of NO synthase, leading to NO-mediated nitrosylation of Na(V)1.5 and to induction of the late Na(+) current. We also show that the antianginal drug ranolazine can abolish CO-induced early after-depolarizations, highlighting a novel approach to the treatment of CO-induced arrhythmias.

The application of Regional Climate Model output for the simulation of high-mountain permafrost scenarios

This study investigates the possibilities and limitations of using Regional Climate Model (RCM) output for the simulation of alpine permafrost scenarios. It focuses on the general problem of scale mismatch between RCMs and impact models and, in particular, the special challenges that arise when driving an impact model in topographically complex high-mountain environments with the output of an RCM. Two approaches are introduced that take into account the special difficulties in such areas, and thus enable the use of RCM for alpine permafrost scenario modelling. Intended as an initial example, they are applied at the area of Corvatsch (Upper Engadine, Switzerland) in order to demonstrate and discuss the application of the two approaches, rather than to provide an assessment of future changes in permafrost occurrence. There are still many uncertainties and inaccuracies inherent in climate and impact models, which increase when driving one model with the output of the other. Nevertheless, our study shows that the use of RCMs offers new and promising perspectives for the simulation of high-mountain permafrost scenarios

Premature impairment of methylation pathway and cardiac metabolic dysfunction in fa/fa obese Zucker rats

Increasing evidence suggests that obesity is a chronic inflammatory disease, in which adipose tissue is involved in a network of endocrine signals to modulate energy homeostasis. These oxidative-inflammatory pathways, which are associated with cardiovascular complications, are also observed during the aging process. In this study, we investigated the interaction between aging and the development of obesity in a hyperphagic rat model. Metabolic profiles of the liver, white adipose tissue (WAT) and heart from young and adult Zucker lean (fa/+) and obese (fa/fa) rats were characterized using a (1)H NMR-based metabonomics approach. We observed premature metabolic modifications in all studied organs in obese animals, some of which were comparable to those observed in adult lean animals. In the cardiac tissue, young obese rats displayed lower lactate and scyllo-inositol levels associated with higher creatine, choline and phosphocholine levels, indicating an early modulation of energy and membrane metabolism. An early alteration of the hepatic methylation and transsulfuration pathways in both groups of obese rats indicated that these pathways were affected before diabetic onset. These findings therefore support the hypothesis that obesity parallels some metabolic perturbations observed in the aging process and provides new insights into the metabolic modifications occurring in pre-diabetic state.

Task design and second language performance: the effect of narrative type on learner output

This article reports on a detailed empirical study of the way narrative task design influences the oral performance of second-language (L2) learners. Building on previous research findings, two dimensions of narrative design were chosen for investigation: narrative complexity and inherent narrative structure. Narrative complexity refers to the presence of simultaneous storylines; in this case, we compared single-story narratives with dual-story narratives. Inherent narrative structure refers to the order of events in a narrative; we compared narratives where this was fixed to others where the events could be reordered without loss of coherence. Additionally, we explored the influence of learning context on performance by gathering data from two comparable groups of participants: 60 learners in a foreign language context in Teheran and 40 in an L2 context in London. All participants recounted two of four narratives from cartoon pictures prompts, giving a between-subjects design for narrative complexity and a within-subjects design for inherent narrative structure. The results show clearly that for both groups, L2 performance was affected by the design of the task: Syntactic complexity was supported by narrative storyline complexity and grammatical accuracy was supported by an inherently fixed narrative structure. We reason that the task of recounting simultaneous events leads learners into attempting more hypotactic language, such as subordinate clauses that follow, for example, while, although, at the same time as, etc. We reason also that a tight narrative structure allows learners to achieve greater accuracy in the L2 (within minutes of performing less accurately on a loosely structured narrative) because the tight ordering of events releases attentional resources that would otherwise be spent on finding connections between the pictures. The learning context was shown to have no effect on either accuracy or fluency but an unexpectedly clear effect on syntactic complexity and lexical diversity. The learners in London seem to have benefited from being in the target language environment by developing not more accurate grammar but a more diverse resource of English words and syntactic choices. In a companion article (Foster & Tavakoli, 2009) we compared their performance with native-speaker baseline data and see that, in terms of nativelike selection of vocabulary and phrasing, the learners in London are closing in on native-speaker norms. The study provides empirical evidence that L2 performance is affected by task design in predictable ways. It also shows that living within the target language environment, and presumably using the L2 in a host of everyday tasks outside the classroom, confers a distinct lexical advantage, not a grammatical one.

Conditioning model output statistics of regional climate model precipitation on circulation patterns

Dynamical downscaling of Global Climate Models (GCMs) through regional climate models (RCMs) potentially improves the usability of the output for hydrological impact studies. However, a further downscaling or interpolation of precipitation from RCMs is often needed to match the precipitation characteristics at the local scale. This study analysed three Model Output Statistics (MOS) techniques to adjust RCM precipitation; (1) a simple direct method (DM), (2) quantile-quantile mapping (QM) and (3) a distribution-based scaling (DBS) approach. The modelled precipitation was daily means from 16 RCMs driven by ERA40 reanalysis data over the 1961–2000 provided by the ENSEMBLES (ENSEMBLE-based Predictions of Climate Changes and their Impacts) project over a small catchment located in the Midlands, UK. All methods were conditioned on the entire time series, separate months and using an objective classification of Lamb's weather types. The performance of the MOS techniques were assessed regarding temporal and spatial characteristics of the precipitation fields, as well as modelled runoff using the HBV rainfall-runoff model. The results indicate that the DBS conditioned on classification patterns performed better than the other methods, however an ensemble approach in terms of both climate models and downscaling methods is recommended to account for uncertainties in the MOS methods.

Sustained striatal activity predicts eudaimonic well-being and cortisol output

Eudaimonic well-being—a sense of purpose, meaning, and engagement with life—is protective against psychopathology and predicts physical health, including lower levels of the stress hormone cortisol. Although it has been suggested that the ability to engage the neural circuitry of reward may promote well-being and mediate the relationship between well-being and health, this hypothesis has remained untested. To test this hypothesis, we had participants view positive, neutral, and negative images while fMRI data were collected. Individuals with sustained activity in the striatum and dorsolateral prefrontal cortex to positive stimuli over the course of the scan session reported greater well-being and had lower cortisol output. This suggests that sustained engagement of reward circuitry in response to positive events underlies well-being and adaptive regulation of the hypothalamic-pituitary-adrenal axis.

Perceived helplessness is associated with individual differences in the central motor output system

Learned helplessness is a maladaptive response to uncontrollable stress characterized by impaired motor escape responses, reduced motivation and learning deficits. There are important individual differences in the likelihood of becoming helpless following exposure to uncontrollable stress but little is known about the neural mechanisms underlying these individual differences. Here we used structural MRI to measure gray and white matter in individuals with chronic pain, a population at high risk for helplessness due to prolonged exposure to a poorly controlled stressor (pain). Given that self-reported helplessness is predictive of treatment outcomes in chronic pain, understanding such differences might provide valuable clinical insight. We found that the magnitude of self-reported helplessness correlated with cortical thickness in the supplementary motor area (SMA) and midcingulate cortex, regions implicated in cognitive aspects of motor behavior. We then examined the white matter connectivity of these regions and found that fractional anisotropy of connected white matter tracts along the corticospinal tract was associated with helplessness and mediated the relationship between SMA cortical thickness and helplessness. These data provide novel evidence that links individual differences in the motor output pathway with perceived helplessness over a chronic and poorly controlled stressor.