What is the role of distributed energy resources under scenarios of greenhouse gas reductions? A specific focus on combined heat and power systems in the industrial and commercial sectors.

Combined heat and power (CHP) is promoted as an economical, energy-efficient option for reducing air emissions, mitigating carbon emissions and reducing reliance on grid electricity. However, its potential benefits have only been analyzed within the context of the current energy system. To fully examine the viability of CHP as a clean-technology alternative, its growth must be analyzed considering how the energy sector may transform under the influence of various technological and policy drivers that are specifically geared toward limiting greenhouse gas (GHG) emissions. Scenarios were developed through a bottom-up technology model of the U.S. energy system to determine the impacts on CHP development and both system-wide and sectoral GHG and air pollutant emissions. Various scenarios were considered, from CO2 emissions reductions in the electric generating units (EGU) sector to GHG reductions across the whole energy system while considering levels of CHP investment. The largest CHP investments were observed in scenarios that limited CO2 emission from the EGU sector alone. The investments were scaled back in the scenarios that incorporated energy system level GHG reductions. The energy system level reduction scenarios yielded rapid transformation of the EGU sector towards zeroemissions technologies as reliance on electricity increases with the electrification of the many end-use sectors such as buildings, transportation and industrial sectors, reducing investment in CHP. The prime mover and fuel choice heavily influenced the air pollutant emissions resulting in trade-offs among pollutants including GHG emissions. The results suggest that CHP could play a role in a future low-carbon energy system, but that role diminishes as carbon reduction targets increase.

Evolution of the United States Energy System and Related Emissions under Varying Social and Technological Development Paradigms: Plausible Scenarios for Use in Robust Decision Making.

The energy system is the primary source of air pollution. Thus, evolution of the energy system into the future will affect society's ability to maintain air quality. Anticipating this evolution is difficult because of inherent uncertainty in predicting future energy demand, fuel use, and technology adoption. We apply scenario planning to address this uncertainty, developing four very different visions of the future. Stakeholder engagement suggested that technological progress and social attitudes toward the environment are critical and uncertain factors for determining future emissions. Combining transformative and static assumptions about these factors yields a matrix of four scenarios that encompass a wide range of outcomes. We implement these scenarios in the U.S. Environmental Protection Agency MARKet ALlocation (MARKAL) model. Results suggest that both shifting attitudes and technology transformation may lead to emission reductions relative to the present, even without additional policies. Emission caps, such as the Cross-State Air-Pollution Rule, are most effective at protecting against future emission increases. An important outcome of this work is the scenario-implementation approach, which uses technology-specific discount rates to encourage scenario-specific technology and fuel choices. End-use energy demands are modified to approximate societal changes. This implementation allows the model to respond to perturbations in manners consistent with each scenario.

Non-convulsive status epilepticus: mimics and chameleons.

Non-convulsive status epilepticus (NCSE) is an enigmatic condition with protean manifestations. It often goes unrecognised, leading to delays in its diagnosis and treatment. The principal reason for such delay is the failure to consider and request an electroencephalogram (EEG), although occasional presentations have no scalp or surface electroencephalographic correlate. In certain settings with limited EEG availability, particularly out-of-hours, clinicians should consider treating without an EEG. Patients need a careful risk-benefit analysis to assess the risks of neuronal damage and harm versus the risks of adverse effects from various intensities of therapeutic intervention. Specialists in EEG, intensive care or epilepsy are invaluable in the management of patients with possible NCSE.

Hidden in plain sight: Non-convulsive status epilepticus-Recognition and management.

Non-convulsive status epilepticus (NCSE) is an electroclinical state associated with an altered level of consciousness but lacking convulsive motor activity. It can present in a multitude of ways, but classification based on the clinical presentation and electroencephalographic appearances assists in determining prognosis and planning treatment. The aggressiveness of treatment should be based on the likely prognosis and the underlying cause of the NCSE.

Role of natural gas in meeting an electric sector emissions reduction strategy and effects on greenhouse gas emissions.

With advances in natural gas extraction technologies, there is an increase in the availability of domestic natural gas, and natural gas is gaining a larger share of use as a fuel in electricity production. At the power plant, natural gas is a cleaner burning fuel than coal, but uncertainties exist in the amount of methane leakage occurring upstream in the extraction and production of natural gas. At higher leakage levels, the additional methane emissions could offset the carbon dioxide emissions reduction benefit of switching from coal to natural gas. This analysis uses the MARKAL linear optimization model to compare the carbon emissions profiles and system-wide global warming potential of the U.S. energy system over a series of model runs in which the power sector is required to meet a specific carbon dioxide reduction target across a number of scenarios in which the availability of natural gas changes. Scenarios are run with carbon dioxide emissions and a range of upstream methane emission leakage rates from natural gas production along with upstream methane and carbon dioxide emissions associated with production of coal and oil. While the system carbon dioxide emissions are reduced in most scenarios, total carbon dioxide equivalent emissions show an increase in scenarios in which natural gas prices remain low and, simultaneously, methane emissions from natural gas production are higher.

Early predictors of refractory status epilepticus: an international two-center study.

BACKGROUND AND PURPOSE: Status epilepticus (SE) refractory to first- and second-line antiepileptic drugs carries high mortality. Little is known on early prediction of refractory SE (RSE)­an essential tool for planning appropriate therapy. Our aim was to identify and validate independent early RSE predictors in adults. METHODS: Clinical and laboratory data on consecutive intensive care unit patients with SE from two academic care centers (a derivation data set from a Swiss center and a validation data set from a US center) were assessed. Multivariable analysis was performed with the derivation set to identify RSE predictors at SE onset. Their external validity was evaluated with an independent validation set. Measures of calibration and discrimination were assessed. RESULTS: In all, 302 patients were analyzed (138 with and 164 without RSE), 171 in the derivation data set and 131 in the validation data set. Acute SE etiology, coma/stupor and serum albumin <35 g/l at SE onset were independent predictors for RSE in the derivation data set [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.01-4.07; OR 4.83, 95% CI 2.42-9.68; OR 2.45, 95% CI 1.16-5.16]. The prediction model showed good measures of calibration (Hosmer-Lemesow goodness-of-fit test P = 0.99) and discrimination (area under the receiver operating characteristic curve 0.8) on the derivation data set­results that were similar in the validation data set (Hosmer-Lemeshow P = 0.24; area under the receiver operating characteristic curve 0.73). CONCLUSIONS: This study confirms the independent prognostic value of readily available parameters for early RSE prediction. Prospective studies are needed to identify additional robust predictors, which could be added to the proposed model for further optimization towards a reliable prediction scoring system.

Uncovering clinical and radiological associations of triphasic waves in acute encephalopathy: a case-control study.

BACKGROUND AND PURPOSE: Triphasic waves (TWs) are archetypal waveforms seen on electroencephalography (EEG) in some forms of encephalopathy. Their particular underlying pathological substrates are largely unexplored. This case-control study was designed to identify and quantify specific clinical and neuroradiological associations underlying TWs and to determine if TWs predicate outcome. METHODS: From 2004 to 2012, adult encephalopathic patients with TWs (cases) were matched 1:1 with encephalopathic patients without TWs (controls) by Glasgow Coma Scale (GCS) and the frequency range of EEG background activity. Clinical characteristics, neuroimaging and outcomes were assessed. RESULTS: The mean age of 190 patients (95 with and 95 without TWs) was 66.6 years (±15.6). In multivariable analyses, patients with TWs had significantly higher odds for liver insufficiency [odds ratio (OR) = 8.10, 95% confidence interval (CI) 1.98-33.08], alcohol abuse (OR = 3.65, 95% CI 1.25-10.63), subcortical brain atrophy (OR = 2.82, 95% CI 1.39-5.71) and respiratory tract infections (OR = 1.28, 95% CI 1.01-4.71). With each additional independent predictor, the odds increased for the occurrence of TWs (1 predictor, OR = 2.40, 95% CI 1.16-5.13; ≥2 predictors, OR = 9.20, 95% CI 3.27-25.62). Mortality was 15% and tended to be higher in patients with TWs (19% with vs. 11% without TWs). CONCLUSIONS: Alcohol abuse, liver insufficiency, infections and subcortical brain atrophy were independently associated with TWs in patients matched for clinical and EEG features of encephalopathy. These associations strengthen the hypothesis that TWs evolve from an interplay of pathological neurostructural, metabolic and toxic conditions. When matched for EEG background activity and GCS, TWs were not associated with death.

Electroencephalographic sleep elements and outcome in acute encephalopathic patients: a 4-year cohort study.

BACKGROUND AND PURPOSE: Acute encephalopathy in hospitalized patients is common and associated with high mortality. Preservation of physiological sleep has been associated with favorable outcomes in acute brain injury. It is hypothesized that electroencephalographic presence of sleep elements is associated with good outcome in encephalopathic adults. METHODS: This observational study was performed at an academic tertiary medical care center. Clinical data, electroencephalogram (EEG) characteristics and outcome of critically ill patients with acute encephalopathy were assessed. EEGs were interpreted regarding the presence of sleep elements (K-complexes, vertex sharp-waves and sleep spindles). Associations between sleep elements and outcome (graded by the Glasgow Outcome Scale, GOS) were analyzed. RESULTS: One hundred and forty-two consecutive patients with a median age of 64.5 years (range 18-98) and mean Glasgow Coma Scale 10.4 (± 3.8) were included. Leading etiologies were infections (47.2%), intracranial hemorrhages (14.1%) and ischaemic strokes (10.6%). All EEGs demonstrated encephalopathy patterns and 38% had ≥ 1 sleep element (27.5% K-complexes, 31.7% vertex sharp-waves and 33.8% sleep spindles). Patients without sleep elements were older (P = 0.010) and septic shock was more common (P = 0.014). Amongst sleep elements, K-complexes were significantly associated with good outcome, even after adjusting for possible confounders (odds ratio for GOS 5 = 2.79, 95% confidence interval 1.16-6.69) and without significant effect modification across subgroups. CONCLUSIONS: Whilst EEG sleep elements were detected more frequently in patients with favorable outcome, only K-complexes were significantly and independently associated with good outcome in intensive care unit patients with acute encephalopathy, findings that need to be confirmed in larger prospective studies.

Hyperhomocysteinemia-Induced Alterations in Protein Expression and Oxidative Stress Parameters in Rat Heart.

Hyperhomocysteinemia (HHcy) is considered an independent risk factor of cardiovascular diseases. Among the proposed mechanisms underlying homocysteine toxicity are altered protein expression and induction of oxidative stress. In the present study, we explored protein abundance and parameters related to oxidative stress in heart homogenates of rats exposed to chronic mild HHcy. Using two-dimensional gel electrophoresis followed by MALDI-TOF/TOF mass spectrometry 22 altered proteins (6 upregulated and 14 downregulated) were identified. For eight proteins the altered abundances were validated by Western blot analysis. Identified proteins are primarily involved in energy metabolism (mainly enzymes of glycolysis, pyruvate dehydrogenase complex, citric acid cycle, and ATP synthase), cardiac muscle contraction (alpha-actin and myosin light chains), stress response (heat-shock protein beta1 and alphaB-crystallin) and antioxidant defense (glutathione peroxidase 1). Diminished antioxidant defense was confirmed by decreases in total antioxidant capacity and GSH/GSSG ratio. Consistent with the decline in enzymatic and non-enzymatic antioxidant defense the protein oxidative modification, as determined by tyrosine nitration, was significantly increased. These findings suggest that both, altered protein expression and elevated oxidative stress contribute to cardiovascular injury caused by HHcy. Keywords: Homocysteine, Heart, Protein abundance, Antioxidant capacity, Nitrotyrosines.

Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene.

Mammalian cytochrome c oxidase (COX) catalyses the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane. Mitochondrial DNA (mtDNA) encodes three COX subunits (I-III) and nuclear DNA (nDNA) encodes ten. In addition, ancillary proteins are required for the correct assembly and function of COX (refs 2, 3, 4, 5, 6). Although pathogenic mutations in mtDNA-encoded COX subunits have been described, no mutations in the nDNA-encoded subunits have been uncovered in any mendelian-inherited COX deficiency disorder. In yeast, two related COX assembly genes, SCO1 and SCO2 (for synthesis of cytochrome c oxidase), enable subunits I and II to be incorporated into the holoprotein. Here we have identified mutations in the human homologue, SCO2, in three unrelated infants with a newly recognized fatal cardioencephalomyopathy and COX deficiency. Immunohistochemical studies implied that the enzymatic deficiency, which was most severe in cardiac and skeletal muscle, was due to the loss of mtDNA-encoded COX subunits. The clinical phenotype caused by mutations in human SCO2 differs from that caused by mutations in SURF1, the only other known COX assembly gene associated with a human disease, Leigh syndrome.

Advancing sustainable bioenergy: evolving stakeholder interests and the relevance of research.

The sustainability of future bioenergy production rests on more than continual improvements in its environmental, economic, and social impacts. The emergence of new biomass feedstocks, an expanding array of conversion pathways, and expected increases in overall bioenergy production are connecting diverse technical, social, and policy communities. These stakeholder groups have different-and potentially conflicting-values and cultures, and therefore different goals and decision making processes. Our aim is to discuss the implications of this diversity for bioenergy researchers. The paper begins with a discussion of bioenergy stakeholder groups and their varied interests, and illustrates how this diversity complicates efforts to define and promote "sustainable" bioenergy production. We then discuss what this diversity means for research practice. Researchers, we note, should be aware of stakeholder values, information needs, and the factors affecting stakeholder decision making if the knowledge they generate is to reach its widest potential use. We point out how stakeholder participation in research can increase the relevance of its products, and argue that stakeholder values should inform research questions and the choice of analytical assumptions. Finally, we make the case that additional natural science and technical research alone will not advance sustainable bioenergy production, and that important research gaps relate to understanding stakeholder decision making and the need, from a broader social science perspective, to develop processes to identify and accommodate different value systems. While sustainability requires more than improved scientific and technical understanding, the need to understand stakeholder values and manage diversity presents important research opportunities.

Why mitochondria are excellent targets for cancer therapy.

New insights into cancer cells - specific biological pathways are urgently needed to promote development of exactly targeted therapeutics. The role of oncoproteins and tumor suppressor proteins in proliferative signaling, cell cycle regulation and altered adhesion is well established. Chemicals, viruses and radiation are also generally accepted as agents that commonly induce mutations in genes encoding these cancer-inducing proteins, thereby giving rise to cancer. More recent evidence indicates the importance of two additional key factors imposed on proliferating cells - hypoxia and/or lack of glucose. These two additional triggers can initiate and promote the process of malignant transformation, when a low percentage of cells escape cellular senescence. Disregulated cell proliferation leads to formation of cellular masses that extend beyond the resting vasculature, resulting in oxygen and nutrient deprivation. Resulting hypoxia triggers a number of critical adaptations that enable cancer cell survival. The process of apoptosis is suppressed and glucose metabolism is altered. Recent investigations suggest that oxygen depletion stimulates mitochondria to compensate increased reactive oxygen species (ROS). It activates signaling pathways, such as hypoxia-inducible factor 1, that promote cancer cell survival and tumor growth. During the last decade, mitochondria have become key organelles involved in chemotherapy-induced apoptosis. Therefore, the relationship between mitochondria, ROS signaling and activation of survival pathways under hypoxic conditions has been the subject of increased study. Insights into mechanisms involved in ROS signaling may offer novel ways to facilitate discovery of cancer-specific therapies.

Psychogenic amnesia and self-identity: a multimodal functional investigation.

BACKGROUND: Patients with psychogenic amnesia generally suffer from episodic memory deficits associated with an impairment of self-identity. While the first is generally attributed to limbic dysfunction, the latter might be related to posterior parietal cortex. METHODS AND RESULTS: In a patient with acute repetitive psychogenic amnesia, three different functional investigations (fMRI, electrical-neuroimaging, PET) during both resting-state and a behavioural paradigm testing 'time-travel' showed left posterior parietal activation, unlike in 12 control subjects. CONCLUSION: Impairment of self-identity and episodic memory in psychogenic amnesia may be associated with functional alterations of left posterior parietal cortex.

Grey hair: clinical investigation into changes in hair fibres with loss of pigmentation in a photoprotected population.

Loss of pigmentation in hair fibres is one of the most obvious phenotypic changes with ageing and has been a topic of increasing interest in the study of follicle biology. The onset of greying brings cosmetic complaints that grey fibres are wild or difficult to manage. Of course, these perceptions may be the consequence of visual obviousness rather than underlying physical or chemical differences. Although several studies have compared pigmented and unpigmented fibres, few have tried to control genetic and ethnic difference as well as extrinsic factors such as photoexposure and chemical treatment. We have recruited subjects with salt-and-pepper hair from a population of Old Order Mennonites who, for cultural reasons, are not only prohibited from chemically treating their hair but also limit their exposure to sunlight. Hair samples were examined for elemental composition, surface energy, Young's modulus, break stress, bending modulus, shear modulus and water sorption/desorption isotherm. The parameters were evaluated statistically for global differences, individual differences and typical individual differences. Consistent with previous published literature, few global differences were found between pigmented and unpigmented hair across the population. We do find that many individual subjects had differences between pigmented and unpigmented fibres. These differences tend to be more pronounced in bulk than in surface properties. The small differences in mechanical properties and moisture uptake and loss lend support to the perception by consumers that grey hair is wilder, drier and less manageable.

Transportation emissions scenarios for New York City under different carbon intensities of electricity and electric vehicle adoption rates.

Like many cities around the world, New York City is establishing policies to reduce CO2 emissions from all energy sectors by 2050. Understanding the impact of varying degrees of electric vehicle adoption and CO2 intensities on emissions reduction in the city is critical. Here, using a technology-rich, bottom-up, energy system optimization model, we analyse the cost and air emissions impacts of New York City's proposed CO2 reduction policies for the transportation sector through a scenario framework. Our analysis reveals that the electrification of light-duty vehicles at earlier periods is essential for deeper reductions in air emissions. When further combined with energy efficiency improvements, these actions contribute to CO2 reductions under the scenarios of more CO2-intense electricity. Substantial reliance on fossil fuels and a need for structural change pose challenges to cost-effective CO2 reductions in the transportation sector. Here we find that uncertainties associated with decarbonization of the electric grid have a minimum influence on the cost-effectiveness of CO2 reduction pathways for the transportation sector.

Antiepileptic drugs modify power of high EEG frequencies and their neural generators.

BACKGROUND: The clinical and molecular effects of antiepileptic drugs (AEDs) have been extensively investigated. Much less is known about their effects on human electrophysiology. METHODS: Topographic analysis in the frequency domain has been used to analyze 104 electroencephalogram (EEG) epochs of 52 patients presenting with first-ever generalized seizure, with normal MRI and EEG. Patients were treated with valproate, arbamazepine, or lamotrigine in monotherapy (each group n = 13). Thirteen patients without medication served as a control group. RESULTS: Carbamazepine and lamotrigine, both sodium-channel modulators, altered brain topography in the gamma range in the same frequency bands (50-60 Hz). Valproate, which has multiple actions on sodium and calcium channels as well as GABA turnover, modified brain topography in the low gamma range (30-40 Hz). No such changes were found in the control group. For all AEDs, the neural generators were shifted more anteriorly in medial temporal through to inferior frontal regions. CONCLUSION: Decreased gamma-power and anterior shift of neural generators after AED introduction reflect AED influence on human electrophysiology.

Understanding Technology, Fuel, Market and Policy Drivers for New York State's Power Sector Transformation.

A thorough understanding of the drivers that affect the emission levels from electricity generation, support sound design and the implementation of further emission reduction goals are presented here. For instance, New York State has already committed a transition to 100% clean energy by 2040. This paper identifies the relationships among driving factors and the changes in emissions levels between 1990 and 2050 using the logarithmic mean divisia index analysis. The analysis relies on historical data and outputs from techno-economic-energy system modeling to elude future power sector pathways. Three scenarios, including a business-as-usual scenario and two policy scenarios, explore the changes in utility structure, efficiency, fuel type, generation, and emission factors, considering the non-fossil-based technology options and air regulations. We present retrospective and prospective analysis of carbon dioxide, sulfur dioxide, nitrogen oxide emissions for the New York State's power sector. Based on our findings, although the intensity varies by period and emission type, in aggregate, fossil fuel mix change can be defined as the main contributor to reduce emissions. Electricity generation level variations and technical efficiency have relatively smaller impacts. We also observe that increased emissions due to nuclear phase-out will be avoided by the onshore and offshore wind with a lower fraction met by solar until 2050.

Incorporating upstream emissions into electric sector nitrogen oxide reduction targets.

Electricity production is a major source of air pollutants in the U.S. Policies to reduce these emissions typically result in the power industry choosing to apply controls or switch to fuels with lower combustion emissions. However, the life-cycle emissions associated with various fuels can differ considerably, potentially impacting the effectiveness of fuel switching. Life-cycle emissions include emissions from extracting, processing, transporting, and distributing fuels, as well as manufacturing and constructing new generating capacity. The field of life-cycle analysis allows quantification of these emissions. While life-cycle emissions are often considered in greenhouse gas mitigation targets, they generally have not been included in air quality policymaking. We demonstrate such an approach, examining a hypothetical electric sector emission reduction target for nitrogen oxides (NOx) using the Global Change Assessment Model with U.S. state-level resolution. When only power plant emissions are considered in setting a NOx emission reduction target, fuel switching leads to an increase in upstream emissions that offsets 5% of the targeted reductions in 2050. When fuel extraction, processing, and transport emissions are included under the reduction target, accounting for 20% of overall NOx reduction goal, the resulting control strategy meets the required reductions and does so at 35% lower cost by 2050. However, manufacturing and construction emissions increase and offset up to 7% of NOx reductions in electric sector, indicating that it may be beneficial to consider these sources as well. Assuming no legal obstacles exist, life-cycle-based approaches could be implemented by allowing industry to earn reduction credits for reducing upstream emissions. We discuss some of the limitations of such an approach, including the difficulty in identifying the location of upstream emissions, which may occur across regulatory authorities or even outside of the U.S.

A randomized trial comparing the efficacy and safety of imiglucerase (Cerezyme) infusions every 4 weeks versus every 2 weeks in the maintenance therapy of adult patients with Gaucher disease type 1.

Imiglucerase (Cerezyme) has been the standard of care for treatment of Gaucher disease, a lysosomal storage disorder resulting from deficiency of glucocerebrosidase, since its approval in 1994. Infusions are typically given once every 2 weeks. However, many patients have expressed a desire for less frequent infusions as a matter of convenience. This clinical study assessed the safety and efficacy of intravenous imiglucerase infused once every 4 weeks (Q4) compared to once every 2 weeks (Q2) at the same total monthly dose in adult patients with clinically stable Gaucher disease type 1 (GD1). This was a 24-month, open-label, randomized, Phase 4, dose-frequency study conducted in 25 centers worldwide. Patients receiving imiglucerase were randomized to receive their monthly dose biweekly (n=33) or every 4 weeks (n=62). Changes from baseline in hemoglobin, platelets, liver and spleen volumes, bone crisis, and bone disease comprised a predefined composite endpoint; achievement or maintenance of established Gaucher disease therapeutic goals comprised a secondary endpoint. Sixty-three percent of Q4- and 81% of Q2-treated patients met the composite endpoint at Month 24; 89% of Q4- and 100% of Q2-treated patients met the therapeutic goals-based endpoint. The frequency of related adverse events was comparable between treatment groups. This study suggests that with comprehensive monitoring, a Q4 imiglucerase infusion regimen may be a safe and effective treatment option for the majority of clinically stable adult patients with GD1 but may not be appropriate for all GD1 patients. Continued monitoring in patients treated with Q4 dosing is required to assess long-term effectiveness.