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ObjectiveTo examine the relationship between midlife milk intake and Parkinson disease (PD) incidence through associations with substantia nigra (SN) neuron density and organochlorine pesticide exposure in decedent brains from the Honolulu-Asia Aging Study.MethodsMilk intake data were collected from 1965 to 1968 in 449 men aged 45-68 years with postmortem examinations from 1992 to 2004. Neuron density (count/mm(2)) was measured in quadrants from a transverse section of the SN. Additional measures included brain residues of heptachlor epoxide, an organochlorine pesticide found at excessively high levels in the milk supply in Hawaii in the early 1980s.ResultsNeuron density was lowest in nonsmoking decedents who consumed high amounts of milk (>16 oz/d). After removing cases of PD and dementia with Lewy bodies, adjusted neuron density in all but the dorsomedial quadrant was 41.5% lower for milk intake >16 oz/d vs intake that was less (95% confidence interval 22.7%-55.7%, p < 0.001). Among those who drank the most milk, residues of heptachlor epoxide were found in 9 of 10 brains as compared to 63.4% (26/41) for those who consumed no milk (p = 0.017). For those who were ever smokers, an association between milk intake and neuron density was absent.ConclusionsMilk intake is associated with SN neuron loss in decedent brains unaffected by PD. Whether contamination of milk with organochlorine pesticides has a role in SN neurodegeneration warrants further study.

We explore the operations, balancing requirements, and costs of the Western Electricity Coordinating Council power system under a stringent greenhouse gas emission reduction target. We include sensitivities for technology costs and availability, fuel prices and emissions, and demand profile. Meeting an emissions target of 85% below 1990 levels is feasible across a range of assumptions, but the cost of achieving the goal and the technology mix are uncertain. Deployment of solar photovoltaics is the main driver of storage deployment: the diurnal periodicity of solar energy availability results in opportunities for daily arbitrage that storage technologies with several hours of duration are well suited to provide. Wind output exhibits seasonal variations and requires storage with a large energy subcomponent to avoid curtailment. The combination of low-cost solar technology and advanced battery technology can provide substantial savings through 2050, greatly mitigating the cost of climate change mitigation. Policy goals for storage deployment should be based on the function storage will play on the grid and therefore incorporate both the power rating and duration of the storage system. These goals should be set as part of overall portfolio development, as system flexibility needs will vary with the grid mix.

© 2015 The Author(s) Jurisdictions throughout the world are contemplating greenhouse gas (GHG) mitigation strategies that will enable meeting long-term GHG targets. Many jurisdictions are now focusing on the 2020–2050 timeframe. We conduct an inter-model comparison of nine California statewide energy models with GHG mitigation scenarios to 2050 to better understand common insights across models, ranges of intermediate GHG targets (i.e., for 2030), necessary technology deployment rates, and future modeling needs for the state. The models are diverse in their representation of the California economy: across scenarios with deep reductions in GHGs, annual statewide GHG emissions are 8–46 % lower than 1990 levels by 2030 and 59–84 % lower by 2050 (not including the Wind-Water-Solar model); the largest cumulative reductions occur in scenarios that favor early mitigation; non-hydroelectric renewables account for 30–58 % of electricity generated for the state in 2030 and 30–89 % by 2050 (not including the Wind-Water-Solar model) ; the transportation sector is decarbonized using a mix of energy efficiency gains and alternative-fueled vehicles; and bioenergy is directed almost exclusively towards the transportation sector, accounting for a maximum of 40 % of transportation energy by 2050. Models suggest that without new policies, emissions from non-energy sectors and from high-global-warming-potential gases may alone exceed California’s 2050 GHG goal. Finally, future modeling efforts should focus on the: economic impacts and logistical feasibility of given scenarios, interactive effects between two or more climate policies, role of uncertainty in the state’s long-term energy planning, and identification of pathways that achieve the dual goals of criteria pollutant and GHG emission reduction.

Sustainable biomass can play a transformative role in the transition to a decarbonized economy, with potential applications in electricity, heat, chemicals and transportation fuels. Deploying bioenergy with carbon capture and sequestration (BECCS) results in a net reduction in atmospheric carbon. BECCS may be one of the few cost-effective carbon-negative opportunities available should anthropogenic climate change be worse than anticipated or emissions reductions in other sectors prove particularly difficult. Previous work, primarily using integrated assessment models, has identified the critical role of BECCS in long-term (pre- or post-2100 time frames) climate change mitigation, but has not investigated the role of BECCS in power systems in detail, or in aggressive time frames, even though commercial-scale facilities are starting to be deployed in the transportation sector. Here, we explore the economic and deployment implications for BECCS in the electricity system of western North America under aggressive (pre-2050) time frames and carbon emissions limitations, with rich technology representation and physical constraints. We show that BECCS, combined with aggressive renewable deployment and fossil-fuel emission reductions, can enable a carbon-negative power system in western North America by 2050 with up to 145% emissions reduction from 1990 levels. In most scenarios, the offsets produced by BECCS are found to be more valuable to the power system than the electricity it provides. Advanced biomass power generation employs similar system design to advanced coal technology, enabling a transition strategy to low-carbon energy.

Two experiments assessed the effects of extinguishing a conditioned cue on subsequent context conditioning. Each experiment used a different video-game method where sensors predicted attacking spaceships and participants responded to the sensor in a way that prepared them for the upcoming attack. In Experiment 1 extinction of a cue which signaled a spaceship-attack outcome facilitated subsequent learning when the attack occurred unsignaled. In Experiment 2 extinction of a cue facilitated subsequent learning, regardless of whether the spaceship outcome was the same or different as used in the earlier training. In neither experiment did the extinction context become inhibitory. Results are discussed in terms of current associative theories of attention and conditioning.

One experiment determined the relationship between renewed associative strength and attention. Following cue1-outcome pairings in Context A, cue1 was extinguished in Context B while cue2 was conditioned. On test cue2 was chosen as a predictor of the outcome in Context B. Both cues were chosen equally often as predictors in Context A. Consistent with attributing attention to effective associative strength (as noted in a previous study), participants could locate only cue2 in Context B while both were located in Context A, regardless of having been chosen as a predictor. Attention varied as a function of both cues' associative strengths across contexts.

Background & aimsIron deficiency is often observed in obese individuals. The iron regulatory hormone hepcidin is regulated by iron and cytokines interleukin (IL) 6 and IL1β. We examine the relationship between obesity, circulating levels of hepcidin, and IL6 and IL1β, and other risk factors in patients with nonalcoholic fatty liver disease (NAFLD) with iron deficiency.MethodsWe collected data on 675 adult subjects (>18 years old) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Subjects with transferrin saturation

The United States Department of Energy's SunShot Initiative has set cost-reduction targets of $1/watt for central-station solar technologies. We use SWITCH, a high-resolution electricity system planning model, to study the implications of achieving these targets for technology deployment and electricity costs in western North America, focusing on scenarios limiting carbon emissions to 80% below 1990 levels by 2050. We find that achieving the SunShot target for solar photovoltaics would allow this technology to provide more than a third of electric power in the region, displacing natural gas in the medium term and reducing the need for nuclear and carbon capture and sequestration (CCS) technologies, which face technological and cost uncertainties, by 2050. We demonstrate that a diverse portfolio of technological options can help integrate high levels of solar generation successfully and cost-effectively. The deployment of GW-scale storage plays a central role in facilitating solar deployment and the availability of flexible loads could increase the solar penetration level further. In the scenarios investigated, achieving the SunShot target can substantially mitigate the cost of implementing a carbon cap, decreasing power costs by up to 14% and saving up to $20 billion ($2010) annually by 2050 relative to scenarios with Reference solar costs.

UnlabelledHepcidin regulation is linked to both iron and inflammatory signals and may influence iron loading in nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the relationships among HFE genotype, serum hepcidin level, hepatic iron deposition, and histology in nonalcoholic fatty liver disease (NAFLD). Single-nucleotide polymorphism genotyping for C282Y (rs1800562) and H63D (rs1799945) HFE mutations was performed in 786 adult subjects in the NASH Clinical Research Network (CRN). Clinical, histologic, and laboratory data were compared using nonparametric statistics and multivariate logistic regression. NAFLD patients with C282Y, but not H63D mutations, had lower median serum hepcidin levels (57 versus 65 ng/mL; P = 0.01) and higher mean hepatocellular (HC) iron grades (0.59 versus 0.28; P < 0.001), compared to wild-type (WT) subjects. Subjects with hepatic iron deposition had higher serum hepcidin levels than subjects without iron for all HFE genotypes (P < 0.0001). Hepcidin levels were highest among patients with mixed HC/reticuloendothelial system cell (RES) iron deposition. H63D mutations were associated with higher steatosis grades and NAFLD activity scores (odds ratio [OR], ≥1.4; 95% confidence interval [CI]: >1.0, ≤2.5; P ≤ 0.041), compared to WT, but not with either HC or RES iron. NAFLD patients with C282Y mutations had less ballooning or NASH (OR, ≤0.62; 95% CI: >0.39,

An enduring feature of Christian religious life has been the experience of the demonic. This experience can be found in the New Testament, most obviously in reported encounters with demons, but more centrally in the language of spiritual warfare that pervades much of the Pauline literature. In the Patristic period, these ideas were cemented in the Christian tradition in the writings of the Desert Fathers. A phenomenological understanding of experience holds that percepts have qualities that are inherently given as part of the experience, and that these qualities can be observed through the use of phenomenological concepts. An examination of the writings of the Desert Fathers suggests that one inherent quality of some religious experiences is their externality. Thoughts or feelings within the person are perceived as having an external source, and external threats can take on an embodied quality in perception, as in visions of demonic beings. These experiences have their initial constitution in an Otherness centered in the body. On reflection, it is not surprising that we would find a quality of externality in religious experience. Religion and spirituality deal with our relationship to the broader world around us. Recent phenomenological writings by Levinas and Marion have begun to recover the importance of externality, however, they neglect aspects of demonic experiences such as their negative valence. Critics of the demonic have tried hard to expel the idea from Western consciousness, pointing to tragic experiences in early modern history and the apparent need to posit the existence of immaterial entities. However, a careful phenomenological and historical analysis casts serious doubt on this modernist picture. The abandonment of the demonic in much of Christian religious thought and practice carries negative consequences, as it invalidates the external quality of many difficult religious experiences. A recovery of the concept of the demonic would help us better understand the phenomenology of religious life.

Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies; however, whether inhibition of mTOR signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders. These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases.