Chronic opioid pretreatment potentiates the sensitization of fear learning by trauma.

Despite the large comorbidity between PTSD and opioid use disorders, as well as the common treatment of physical injuries resulting from trauma with opioids, the ability of opioid treatments to subsequently modify PTSD-related behavior has not been well studied. Using the stress-enhanced fear learning (SEFL) model for PTSD, we characterized the impact of chronic opioid regimens on the sensitization of fear learning seen following traumatic stress in mice. We demonstrate for the first time that chronic opioid pretreatment is able to robustly augment associative fear learning. Highlighting aversive learning as the cognitive process mediating this behavioral outcome, these changes were observed after a considerable period of drug cessation, generalized to learning about multiple aversive stimuli, were not due to changes in stimulus sensitivity or basal anxiety, and correlated with a marker of synaptic plasticity within the basolateral amygdala. Additionally, these changes were not observed when opioids were given after the traumatic event. Moreover, we found that neither reducing the frequency of opioid administration nor bidirectional manipulation of acute withdrawal impacted the subsequent enhancement in fear learning seen. Given the fundamental role of associative fear learning in the generation and progression of PTSD, these findings are of direct translational relevance to the comorbidity between opioid dependence and PTSD, and they are also pertinent to the use of opioids for treating pain resulting from traumas involving physical injuries

Exchange and correlation in molecular wire conductance: non-locality is the key

We study real-time electron dynamics in a molecular junction with a variety of approximations to the electronic structure, toward the ultimate aim of determining what ingredients are crucial for the accurate prediction of charge transport. We begin with real-time, all electron simulations using some common density functionals that differ in how they treat long-range Hartree–Fock exchange. We find that the inclusion or exclusion of nonlocal exchange is the dominant factor determining the transport behavior, with all semilocal contributions having a smaller effect. In order to study nonlocal correlation, we first map our junction onto a simple Pariser–Parr–Pople (PPP) model Hamiltonian. The PPP dynamics are shown to faithfully reproduce the all electron results, and we demonstrate that nonlocal correlation can be readily included in the model space using the generator coordinate method (GCM). Our PPP-GCM simulations suggest that nonlocal correlation has a significant impact on the I-V character that is not captured even qualitatively by any of the common semilocal approximations to exchange and correlation. The implications of our results for transport calculations are discussed.National Science Foundation (U.S.) (CAREER under Grant No. CHE-0547877)David & Lucile Packard Foundation (Fellowship

Underground mining of aggregates. Main report

This report examines the economic feasibility of underground mining for crushed rock aggregates in the UK, but particularly in the London, South East and East of England regions (the South East area of England). These regions import substantial volumes of crushed rock, primarily from the East Midlands and South West regions, requiring relatively long transport distances to market for this bulk commodity. A key part of the research was to determine whether or not aggregate could be produced and delivered to a local market from an underground aggregates operation at a cost comparable with that for production and transport of the commodity from traditional surface quarries located further afield. In essence the investigation asked – could the reduced transport costs compensate for the higher production costs underground so that underground crushed rock aggregates producers can compete with the established Leicestershire and Somerset surface quarries exporting to the South East? Work Programme The research effort involved establishing and verifying cost models for aggregates production, stone processing (sizing and sorting), haulage of product to market, environmental impact mitigation, health and safety, decommissioning and restoration. Another major element of the work was the re-examination of the BGS exploratory borehole and geophysical databases to identify potential areas of crushed rock aggregates resource at depth in the South East area of England. Land use pressure is typically higher in this area of England than elsewhere so another major part of the research was the identification of potential concurrent uses of land around the surface facilities of underground aggregates mines. The value, development costs for specific developments and determination of yields expected, from these uses were estimated. These were also used to investigate potential economic benefits associated with after uses of remediated surface land above potential underground aggregates mines and also for the new underground space that would be created. Key technical issues such as subsidence within relatively heavily populated areas of the South East area of England were also addressed. Economic Results The discounted cost of aggregate delivered at a discount rate of 10% was the metric used to appraise the options. This is the price of aggregate that leads to a zero net present value of project cash flows realised over the aggregates project life. The results show that the discounted costs of aggregate delivered to a local South East area of England market from an underground mine producing 3.5 million tonnes per annum (MTPA) of crushed rock aggregates, are in the range of £13.03 per tonne to £13.93 per tonne for the top six prospect locations. These are greater than the corresponding cost for a “reference” quarry in Leicestershire producing 3.5 MTPA (£10.95 per tonne), but lower than a “reference” quarry in Leicestershire producing 1.25 MTPA (£16.48 per tonne). These figures indicate that underground crushed rock aggregate mines located within the South East area of England may be able to compete for a share in the overall market by replacing / displacing aggregate imported from the quarries in Leicestershire and Somerset producing around or less than 1.25 MTPA. The surprise in these figures is not really that the more remote surface quarry has a lower discounted cost of aggregate delivered, but that the values for the quarry and underground mine are so close. The capital intensity for the development of underground aggregates mines was found to be higher than that required for surface quarries of comparable scale, by a factor ranging from 1.33 to 1.65 and thus may represent a disincentive for aggregates operators. Carbon Emissions The total carbon emissions of the ‘reference’ 3.5 MTPA quarry in Leicestershire were estimated at 9.28 kg CO2/tonne aggregate delivered and this is to be compared with carbon emissions for the 150 metre deep underground mines serving the local market which were estimated at 9.31 kg CO2/tonne delivered for a Bletchley prospect using an adit to access the sub-surface and 14.25 kg CO2/tonne delivered for a prospect based on the Chitty bore hole using a shaft. Depth of the mine is a key factor in determination of the relative carbon emissions from each of the underground mining operations considered as electricity consumption for ventilation, pumping and winding is proportional to depth. Recommendations The current research generated seven principal recommendations which are discussed in detail in the concluding section of the report. These are: Appraise policy incentives for underground aggregates mining. Conduct an industry-wide consultation on findings from the current research. Obtain public and stakeholder opinion on new uses for underground space. Conduct research to reducing the energy intensity of mine services. Develop a deep level aggregates-specific drilling campaign. Investigate underground aggregates mines developed from existing surface quarries. Investigate underground aggregates as co-products of industrial minerals mining

Brand equity and willingness to pay for condoms in zimbabwe

<p>Abstract</p> <p>Background</p> <p>Zimbabwe suffers from one of the greatest burdens of HIV/AIDS in the world that has been compounded by social and economic instability in the past decade. However, from 2001 to 2009 HIV prevalence among 15-49 year olds declined from 26% to approximately 14%. Behavior change and condom use may in part explain this decline.</p> <p>PSI-Zimbabwe socially markets the Protector Plus (P+) branded line of condoms. When Zimbabwe converted to a dollar-based economy in 2009, the price of condoms was greatly increased and new marketing efforts were undertaken. This paper evaluates the role of condom marketing, a multi-dimensional scale of brand peceptions (brand equity), and price in condom use behavior.</p> <p>Methods</p> <p>We randomly sampled sexually active men age 15-49 from 3 groups - current P+ users, former users, and free condom users. We compared their brand equity and willingness to pay based on survey results. We estimated multivariable logistic regression models to compare the 3 groups.</p> <p>Results</p> <p>We found that the brand equity scale was positive correlated with willingness to pay and with condom use. Former users also indicated a high willingness to pay for condoms. We found differences in brand equity between the 3 groups, with current P+ users having the highest P+ brand equity. As observed in previous studies, higher brand equity was associated with more of the targeted health behavior, in this case and more consistent condom use.</p> <p>Conclusions</p> <p>Zimbabwe men have highly positive brand perceptions of P+. There is an opportunity to grow the total condom market in Zimbabwe by increasing brand equity across user groups. Some former users may resume using condoms through more effective marketing. Some free users may be willing to pay for condoms. Achieving these objectives will expand the total condom market and reduce HIV risk behaviors.</p

Mismatch repair causes the dynamic release of an essential DNA polymerase from the replication fork

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86887/1/MMI_7841_sm_SuppInfor.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/86887/2/j.1365-2958.2011.07841.x.pd

Major epidemiological changes in sudden infant death syndrome : a 20-year population-based study in the UK

Background Results of case-control studies in the past 5 years suggest that the epidemiology of sudden infant death syndrome (SIDS) has changed since the 1991 UK Back to Sleep campaign. The campaign's advice that parents put babies on their back to sleep led to a fall in death rates. We used a longitudinal dataset to assess these potential changes. Methods Population-based data from home visits have been collected for 369 consecutive unexpected infant deaths (300 SIDS and 69 explained deaths) in Avon over 20 years (1984—2003). Data obtained between 1993 and 1996 from 1300 controls with a chosen “reference” sleep before interview have been used for comparison. Findings Over the past 20 years, the proportion of children who died from SIDS while co-sleeping with their parents, has risen from 12% to 50% (p<0·0001), but the actual number of SIDS deaths in the parental bed has halved (p=0·01). The proportion seems to have increased partly because the Back to Sleep campaign led to fewer deaths in infants sleeping alone—rather than because of a rise in deaths of infants who bed-shared, and partly because of an increase in the number of deaths in infants sleeping with their parents on a sofa. The proportion of deaths in families from deprived socioeconomic backgrounds has risen from 47% to 74% (p=0·003), the prevalence of maternal smoking during pregnancy from 57% to 86% (p=0·0004), and the proportion of pre-term infants from 12% to 34% (p=0·0001). Although many SIDS infants come from large families, first-born infants are now the largest group. The age of infants who bed-share is significantly smaller than that before the campaign, and fewer are breastfed. Interpretation Factors that contribute to SIDS have changed in their importance over the past 20 years. Although the reasons for the rise in deaths when a parent sleeps with their infant on a sofa are still unclear, we strongly recommend that parents avoid this sleeping environment. Most SIDS deaths now occur in deprived families. To better understand contributory factors and plan preventive measures we need control data from similarly deprived families, and particularly, infant sleep environments

Empirical Storm-Time Correction to the International Reference Ionosphere Model E-Region Electron and Ion Density Parameterizations Using Observations from TIMED/SABER

The response of the ionospheric E-region to solar-geomagnetic storms can be characterized using observations of infrared 4.3 micrometers emission. In particular, we utilize nighttime TIMED/SABER measurements of broadband 4.3 micrometers limb emission and derive a new data product, the NO+(v) volume emission rate, which is our primary observation-based quantity for developing an empirical storm-time correction the IRI E-region electron density. In this paper we describe our E-region proxy and outline our strategy for developing the empirical storm model. In our initial studies, we analyzed a six day storm period during the Halloween 2003 event. The results of this analysis are promising and suggest that the ap-index is a viable candidate to use as a magnetic driver for our model