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Objectives: Alcohol dependence leads to dysregulation of the neuroimmune system, but the effects of excessive alcohol consumption on key players of the neuroimmune response after episodic binge drinking in nondependence has not been readily assessed. These studies seek to determine how the neuroimmune system within the hippocampus responds to binge-like consumption prior to dependence or evidence of brain damage. Methods: C57BL/6J mice underwent the drinking in the dark (DID) paradigm to recapitulate binge consumption. Immunohistochemical techniques were employed to determine the effects of ethanol on cytokine and astrocyte responses within the hippocampus. Astrocyte activation was also assessed using qRT-PCR. Results: Our results indicated that binge-like ethanol consumption resulted in a 3.6-fold increase in the proinflammatory cytokine interleukin (IL)-1β immunoreactivity in various regions of the hippocampus. The opposite effect was seen in the anti-inflammatory cytokine IL-10. Binge-like consumption resulted in a 67% decrease in IL-10 immunoreactivity but had no effect on IL-4 or IL-6 compared with the water-drinking control group. Moreover, astrocyte activation occurred following ethanol exposure as GFAP immunoreactivity was increased over 120% in mice that experienced 3 cycles of ethanol binges. PCR analyses indicated that the mRNA increased by almost 4-fold after one cycle of DID, but this effect did not persist in abstinence. Conclusions: Altogether, these findings suggest that binge-like ethanol drinking prior to dependence causes dysregulation to the neuroimmune system. This altered neuroimmune state may have an impact on behavior but could also result in a heightened neuroimmune response that is exacerbated from further ethanol exposure or other immune-modulating events.

The piece uses a model derived from analysing the modern drugs trade where evidence is notoriously difficult to gather, in order to suggest possible applications to the medieval trade in slaves. The piece also looks at the possible role of the slave trade in the early formation of what would become the kingdom of Poland.

Microglia are dynamic cells that have roles in neuronal plasticity as well as in recovery responses following neuronal injury. Although many hypothesize that hyperactivation of microglia contributes to alcohol-induced neuropathology, in other neurodegenerative conditions disruption of normal microglial processes also contributes to neuronal loss, particularly as microglia become dystrophic or dysfunctional. Based on the observation of a striking, abnormal morphology in microglia during binge-like ethanol exposure, the present study investigated the impact of excessive ethanol exposure on microglia number and dystrophic morphology in a model of alcohol dependence that includes neurodegeneration in both adult and adolescent rats. Following 2- and 4-day binge ethanol exposure, the number of microglia was decreased in the hippocampus and the perirhinal and entorhinal cortices of both adult and adolescent rats. Furthermore, a significant number of microglia with a dystrophic morphology were observed in ethanol-exposed tissue, accompanied by a significant decrease in brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Together these findings suggest another means by which microglia may contribute to alcohol-induced neurodegeneration, specifically dystrophic microglia and/or loss of microglia may disrupt homeostatic and recovery mechanisms. These results demonstrate that microglia also degenerate with excessive alcohol exposure, which has important implications for understanding the role of microglia—and specifically their contributions to plasticity and neuronal survival—in neurodegenerative disease.

Nowadays most retrofit decisions are based on reducing CO2 / heating consumption. The aim of this study was to determine the reliability of three tools (RdSAP, SAP and IES) often used to predict these reductions. Three no-fines concrete (NFC) dwellings (C1, C2, and C3) with similar floor area and construction but different occupants were monitored. Key information about the thermal performance of the fabric; the behaviour of the occupants and the energy consumption was collected before and after 110 mm of external wall insulation (EWI) was added. The target was a 30% reduction on energy consumption due to the EWI. However, only C3 decreased it by 30% as expected, C2 only by 14% due to a subtle rebound effect and C1 actually increased consumption by 75%, due to rebound effect. Steady state tools (RdSAP and SAP) were found to be inaccurate in predicting the operational energy consumption of dwellings, only dynamic performance analysis software (IES) was suitable to carry out this type of prediction accurately. However, this type of software requires highly accurate and detailed information regarding: the baseline performance of the fabric, external weather conditions and, most importantly, accurate pre- and post- heating operational habits of the occupants. Few retrofitting projects have the resources and time to gather this information. Unless those are available, the retrofit decisions should be based in a different criteria, rather than using inaccurate SAP or RdSAP energy consumption predictions. The coefficient of heat loss of the fabric of a dwelling is independent of the occupants. SAP was found quick to calculate reasonable predictions of the coefficient, by using accurate fabric data, and to show the impact of different factors on the heat loss of the fabric. Therefore, it could be claimed that the coefficient of heat loss of the fabric is a suitable alternative criteria to make pre-retrofit decisions.

North American leaders recently committed to reducing methane emissions from the oil and gas sector, but information on current emissions from Canadian unconventional developments is lacking. This study examined the incidence of methane in an area of unconventional natural gas development in northwestern Canada. In August to September 2015 we completed almost 8000 km of vehicle-based survey campaigns on public roads dissecting developments that mainly access the Montney formation in northeastern British Columbia. Six survey routes were repeated 3–6 times and brought us past over 1600 unique well pads and facilities developed by more than 50 different operators. To attribute on-road plumes to infrastructural sources we used gas signatures of residual excess concentrations (anomalies above background) less than 500 m downwind from infrastructural sources. All results represent emissions greater than our minimum detection limit of 0.59 g/s at our average detection distance (319 m). Unlike many other developments in the US for which methane measurements have been reported recently, the methane concentrations we measured at surface were close to normal atmospheric levels, except inside natural gas plumes. Roughly 47 % of active wells emitted methane-rich plumes above our minimum detection limit. Abandoned and under-development well sites also emitted methane-rich plumes, but the incidence rate was below that of producing wells. Multiple sites that pre-date the recent unconventional Montney development were found to be emitting, and in general we observed that older infrastructure tended to emit more often (per unit) with comparable severity in terms of measured excess concentrations on-road. We also observed emissions from facilities of various types that were highly repeatable. Emission patterns in this area were best explained by infrastructure age and type. Extrapolating our results across the Montney development, we estimate that the emission sources we located (emitting at a rate > 0.59 g/s) contribute more than 111,800 tonnes of methane annually to the atmosphere. This value exceeds reported bottom-up estimates of 78,000 tonnes for all oil and gas sector sources in British Columbia, of which the Montney represents about 55 % of production. The results also demonstrate that mobile surveys could be used to exhaustively screen developments for super-emitters, because without our intensive 6-fold replication we could have used single-pass sampling to screen 80 % of Montney-related infrastructure. This is the first bottom-up study of fugitive emissions in the Canadian energy sector, and these results can be used to inform policy development in an era of methane emission reduction efforts.

Alcoholism is a highly visible and prevalent issue in the United States. Although binge-drinking is assumed to be a college-age problem, older adults (ages 65 +) consume binge amounts of alcohol and have alcohol use disorders (AUDs). Moreover, individuals with alcohol dependence in their youth often continue to drink as they age. As such, this study tested the hypothesis that the effects of alcohol on hippocampal microglia are exacerbated in aged versus younger rodents in two AUD models. Briefly, adult (2–3 months) and aged (15 + months) Sprague-Dawley rats were administered alcohol or control diet using the Majchrowicz model to study alcohol-induced neurodegeneration. To study the effects of non-dependent binge consumption on microglia, adolescent (6–8 weeks) and aged (18 + months) C57/BL6N were subjected to the Drinking in the Dark paradigm. Microglia number and densitometry were assessed using immunohistochemistry. Hippocampal subregional and model/species-specific effects of alcohol were observed, but overall, aging did not appear to increase the alcohol-induced microglia reactivity as measured by Iba-1 densitometry. However, analysis of microglial counts revealed a significant decrease in the number microglia cells in both the alcohol-induced neurodegeneration and DID model across age groups. In the dentate gyrus, the loss of microglia was exacerbated by aging, particularly in mice after DID, non-dependent model. Using qRT-PCR, the persistence of alcohol and aging effects was assessed following the DID model. Allograft Inflammatory Factor 1 mRNA was increased in both young and aged mice by alcohol exposure; however, only in the aged mice did the alcohol effect persist. Overall, these data imply that the microglial response to alcohol is complex with evidence of depressed numbers of microglia but also increased reactivity with advanced age.

During the next few years, 30 million households and small businesses in the UK will be equipped with a Smart Metering system. Smart meter data could play a central role in the Smart Home ecosystem as well as on the efficient use of the Smart Grid through IoT technologies. This work focuses on methods of acquiring smart meter data from Smart Metering servers and how this data could be utilised directly by domestic consumers and other stakeholders to their benefit, in particular in terms of energy and cost efficiency for the consumer and of stability for the Smart Grid. The steps which need to be followed in order to acquire data from Smart Metering servers using APIs, in particular the REST and the MQTT APIs, are outlined. The visual representation of data streams in near real-time and the post-processing of the smart meter data has led to the development of certain applications which provide customers with a display of their electricity and gas energy consumption as well as the corresponding cost. Moreover, an initial visual display towards an application further utilising the acquired data for the benefit of energy suppliers and energy service companies, using signal processing methods, is provided.

On January 26, 2018, the 23rd annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado. The meeting consisted of plenary sessions with oral presentations and a poster presentation session. There were four plenary sessions that covered a wide range of topics relating to alcohol use: Alcohol and Liver Disease; Alcohol, Inflammation and Immune Response; Alcohol and Organ Injury; Heath Consequences and Alcohol Drinking. The meeting provided a forum for the presentation and discussion of novel research findings regarding alcohol use and immunology.

Psychological depression is frequently linked to alcohol abuse and even serves as key indicators of an alcohol use disorder (AUD). This relationship is supported by preclinical findings in which depression-like phenotypes develop in animals exposed to chronic intermittent ethanol vapor, a common preclinical model of alcohol dependence. However, the emergence of these maladaptive phenotypes following repeated binge-like ethanol drinking remains relatively unexplored. The purpose of this study was to evaluate depression-like behaviors associated with binge-like consumption in mice. Using the drinking-in-the-dark (DID) paradigm, we examined the impact of multiple binge-like cycles (1, 3, or 6) on depression-like behaviors in the forced swim test (FST) and sucrose preference as a test for anhedonia. We also assessed the effect of repeated binge cycles on the consumption of bitter and sweet tastants over a range of concentrations. Results indicated that binge-like ethanol drinking did not lead to depression-like behavior as repeated cycles of DID did not alter sucrose consumption or preference nor did it impact time spent immobile during the FST. Animals that experienced six cycles of DID showed increased quinine consumption and increased quinine preference, which may be indicative of an escalated preference for tastants that resemble the gustatory aspects of ethanol. Interestingly, an unexpected ~20% increase in hypermobility was observed after three cycles of binge-like ethanol drinking. Although the FST is most frequently used to model depression-like behavior, emerging evidence suggests that increased hypermobility during the FST could be indicative of an inability to cope in a stressful situation, suggesting that repeated ethanol exposure in the present experiment transiently enhances stress reactivity.

Known in the West up until now predominantly through the publication of a limited number of his economic writings, E.A. Preobrazhensky has gone down in history primarily as a theorist of the ‘transition period’ in socialist economics and as a prominent victim of Stalin's purges. A new series of his collected works, however, publishing for the first time large quantities of material from his diaries, letters and newspaper work, looks set to transform his reputation, and underline his stature as one of the most original and sympathetic figures produced by the Bolshevik Revolution.

There is a growing body of evidence available to indicate that there is often a discrepancy between the in situ measured thermal performance of a building fabric and the steady-state predicted performance of that fabric, even when the building fabric has been modelled based upon what was actually built. However, much of the work that has been published to date does not fully investigate the validity of the assumptions within the model and whether they fully characterise the building. To investigate this issue, a typical pre-1920’s UK house is modelled in Designbuilder in order to recognise and reduce the gap between modelled and measured energy performance. A model was first built to the specifications of a measured survey of the Salford Energy House, a facility which is housed in a climate controlled chamber. Electric coheating tests were performed to calculate the building’s heat transfer coefficient; a difference of 18.5% was demonstrated between the modelled and measured data, indicating a significant ‘prediction gap’. Accurate measurements of air permeability and U-value were made in-situ; these were found to differ considerably from the standard values used in the initial model. The standard values in the model were modified to reflect these in-situ measurements, resulting in a reduction of the performance gap to 2.4%. This suggests that a better alignment between the modelling and measurement research communities could lead to more accurate models and a better understanding of performance gap issues.

Lenin's Imperialism. The Highest Stage of Capitalism formed part of the canon of mainstream Marxist writing for much of the 20th century, and also represented a critical reference point for Marxist attempts to interpret international relations for much of the same period. At one and the same time both a stinging condemnation of the betrayal of the European working class by their political leaders in 1914, and a synthesis, with some original elements, of existing contemporary Marxist theory on imperialism, Lenin's ‘popular outline’ subsequently (from around the time of the ‘New Left’ onwards) came under increasing fire for being incoherent, irrelevant and overrated. This article revisits both the contemporary genesis of the text, and the question of its longer term pertinence and relevance in the light of capitalism's current crisis.

International audience; Global climate change and a growing population require tackling the reduction in arable land and improving biomass production and seed yield per area under varying conditions. One of these conditions is suboptimal water availability. Here, we review some of the classical approaches to dealing with plant response to drought stress and we evaluate how research on RECEPTOR-LIKE KINASES (RLKs) can contribute to improving plant performance under drought stress. RLKs are considered as key regulators of plant architecture and growth behavior, but they also function in defense and stress responses. The available literature and analyses of available transcript profiling data indeed suggest that RLKs can play an important role in optimizing plant responses to drought stress. In addition, RLK pathways are ideal targets for nontransgenic approaches, such as synthetic molecules, providing a novel strategy to manipulate their activity and supporting translational studies from model species, such as Arabidopsis thaliana, to economically useful crops.

Accumulating evidence indicates that the adolescent hippocampus is highly susceptible to alcohol-induced structural damage and behavioral deficits. Microglia are vitally important brain constituents needed to support and maintain proper neural function; however, alcohol’s effects on microglia have only recently gained attention. The microglial response to alcohol during adolescence has yet to be studied; therefore, we examined hippocampal microglial activation in an adolescence binge alcohol exposure model. Adolescent male Sprague–Dawley rats were administered ethanol 3 times/day for 4 days and were sacrificed 2, 7, and 30 days later. Bromo-deoxy-Uridine was injected 2 days after ethanol exposure to label dividing cells. Microglia morphology was scored using the microglia marker Iba-1, while the extent of microglial activation was examined with ED-1, major histocompatability complex-II (MHC-II), and tumor necrosis factor (TNF)-α expression. Ethanol induced significant morphological change in hippocampal microglia, consistent with activation. In addition, ethanol increased the number of BrdU+ cells throughout all regions of the hippocampus 2 days after the last dose. Confocal microscopy showed that the proliferating BrdU+ cells in each region were Iba-1+ microglia. Importantly, newly born microglia survived and retained their morphological characteristics 30 days after ethanol exposure. Ethanol did not alter hippocampal ED-1, MHC-II, or TNF-α expression, suggesting that a single period of binge ethanol exposure does not induce a full microglial-driven neuroinflammatory response. These results establish that ethanol triggers partial microglial activation in the adolescent hippocampus that persists through early adulthood, suggesting that alcohol exposure during this unique developmental time period has long-lasting consequences.

Excessive alcohol consumption results in neurodegeneration which some hypothesize is caused by neuroinflammation. One characteristic of neuroinflammation is microglial activation, but it is now well accepted that microglial activation may be pro- or anti-inflammatory. Recent work indicates that the Majchrowicz model of alcohol-induced neurodegeneration results in anti-inflammatory microglia, while intermittent exposure models with lower doses and blood alcohol levels produce microglia with a pro-inflammatory phenotype. To determine the effect of a repeated binge alcohol exposure, rats received two cycles of the four-day Majchrowicz model. One hemisphere was then used to assess microglia via immunohistochemistry and while the other was used for ELISAs of cytokines and growth factors. A single binge ethanol exposure resulted in low-level of microglial activation; however, a second binge potentiated the microglial response. Specifically, double binge rats had greater OX-42 immunoreactivity, increased ionized calcium-binding adapter molecule 1 (Iba-1+) cells, and upregulated tumor necrosis factor-α (TNF-α) compared with the single binge ethanol group. These data indicate that prior ethanol exposure potentiates a subsequent microglia response, which suggests that the initial exposure to alcohol primes microglia. In summary, repeated ethanol exposure, independent of other immune modulatory events, potentiates microglial activity.

200 liver tumors in women taking birth control pills have been reported since 1973 when an association between these tumors and oral contraceptive use was 1st suggested. Most tumors have been benign showing histological characteristics of either hepatic cell adenoma or focal nodular hyperplasia. 1 survey found 543 cases of primary liver tumors reported between 1970-1975 of which 91.5% of those in males but only 43.8% of those in females were malignant. Overall 65% of the benign tumors among females were associated with oral contraceptive use but over 80% of benign tumor patients aged 20-30 were pill users. Further evidence of an association is the reported regression of liver tumors after cessation of pill use. However a study of 6 million people found only 1 benign hepatic tumor. Such conflicting results point to the need for an adequate epidemiological study to assess the frequency of tumors in users and nonusers compared with the frequency of oral contraceptive use in the female population. The duration of pill exposure and the type of estrogen used may be relevant to the development of benign liver tumors. Hemoperitoneum or hemorrhage in cases of focal nodular hyperplasia and tumor rupture in hepatic cell adenomas are significantly more frequent in pill users than nonusers. Most "pill-associated" tumors have been solitary and amenable to surgical resection with low mortality. While there is considerable evidence that oral contraceptive use plays a role in the development of hepatic cell adenomas and focal nodular hyperplasia there is less reason to believe the pill is involved in the pathogenesis of primary hepatocellular carcinoma. More research is needed to determine the oncogenic potential of oral contraceptives and the malignant potential of benign tumors.