Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346-Insensitive Nuclear Translocation of GAPDH

The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) signals during cellular stress via several post-translational modifications that change its folding properties, protein-protein interactions and sub-cellular localization. We examined GAPDH properties in acute mouse liver injury due to ethanol and/or acetaminophen (APAP) treatment. Synergistic robust and time-dependent nuclear accumulation and aggregation of GAPDH were observed only in combined, but not individual, ethanol/APAP treatments. The small molecule GAPDH-targeting compound TCH346 partially attenuated liver damage possibly via mitochondrial mechanisms, and independent of nuclear accumulation and aggregation of GAPDH. These findings provide a novel potential mechanism for hepatotoxicity caused by combined alcohol and acetaminophen exposure

Control of an atom laser using feedback

A generalised method of using feedback to control Bose-Einstein condensates is introduced. The condensates are modelled by the Gross-Pitaevskii equation, so only semiclassical fluctations can be suppressed, and back-action from the measurement is ignored. We show that for any available control, a feedback scheme can be found to reduce the energy while the appropriate moment is still dynamic. We demonstrate these schemes by considering a condensate trapped in a harmonic potential that can be modulated in strength and position. The formalism of our feedback scheme also allows the inclusion of certain types of non-linear controls. If the non-linear interaction between the atoms can be controlled via a Feshbach resonance, we show that the feedback process can operate with a much higher efficiency.Comment: 6 pages, 7 figure

The effects of human socioeconomic status and cultural characteristics on urban patterns of biodiversity

ABSTRACT. We present evidence that there can be substantial variation in species richness in residential areas differing in their socioeconomic and cultural characteristics. Many analyses of the impacts of urbanization on biodiversity rely on traditional "urban-to-rural" gradient measures, such as distance from urban center or population density, and thus can fail to account for the ways in which human socioeconomic and cultural characteristics are shaping the human-environment interaction and ecological outcomes. This influence of residential values and economic resources on biodiversity within the urban matrix has implications for human quality of life, for urban conservation strategies, and for urban planning

Evidence of continued injecting drug use after attaining sustained treatment-induced clearance of the hepatitis C virus: implications for reinfection

Background: People who inject drugs (PWID) are at the greatest risk of hepatitis C virus (HCV) infection, yet are often denied immediate treatment due to fears of on-going risk behaviour. Our principal objective was to examine evidence of continued injecting drug use among PWID following successful treatment for HCV and attainment of a sustained viral response (SVR). Methods: PWID who attained SVR between 1992 and June 2012 were selected from the National Scottish Hepatitis C Clinical Database. Hospitalisation and mortality records were sourced for these patients using record linkage techniques. Our primary outcome variable was any hospitalisation or death, which was indicative of injecting drugs post-SVR. Results: The cohort comprised 1170 PWID (mean age at SVR 39.6y; 76% male). The Kaplan Meier estimate of incurring the primary outcome after three years of SVR was 10.59% (95% CI, 8.75–12.79) After adjusting for confounding, the risk of an injection related hospital episode or death post-SVR was significantly increased with advancing year of SVR: AHR:1.07 per year (95% CI, 1.01–1.14), having a pre-SVR acute alcohol intoxication-related hospital episode: AHR:1.83 (95% CI, 1.29–2.60), and having a pre-SVR opiate or injection-related hospital episode: AHR:2.59 (95% CI, 1.84–3.64). Conclusion: Despite attaining the optimal treatment outcome, these data indicate that an increasing significant minority of PWID continue to inject post-SVR at an intensity which leads to either hospitalisation or death and increased risk of reinfection

Efficient precision quantization in AdS/CFT

Understanding finite-size effects is one of the key open questions in solving planar AdS/CFT. In this paper we discuss these effects in the AdS_5xS^5 string theory at one-loop in the world-sheet coupling. First we provide a very general, efficient way to compute the fluctuation frequencies, which allows to determine the energy shift for very general multi-cut solutions. Then we apply this to two-cut solutions, in particular the giant magnon and determine the finite-size corrections at subleading order. The latter are then compared to the finite-size corrections from Luscher-Klassen-Melzer formulas and found to be in perfect agreement.Comment: 32 pages, 5 figures; v2: typos corrected, refs adde

Setting priorities in health care organizations: criteria, processes, and parameters of success

BACKGROUND: Hospitals and regional health authorities must set priorities in the face of resource constraints. Decision-makers seek practical ways to set priorities fairly in strategic planning, but find limited guidance from the literature. Very little has been reported from the perspective of Board members and senior managers about what criteria, processes and parameters of success they would use to set priorities fairly. DISCUSSION: We facilitated workshops for board members and senior leadership at three health care organizations to assist them in developing a strategy for fair priority setting. Workshop participants identified 8 priority setting criteria, 10 key priority setting process elements, and 6 parameters of success that they would use to set priorities in their organizations. Decision-makers in other organizations can draw lessons from these findings to enhance the fairness of their priority setting decision-making. SUMMARY: Lessons learned in three workshops fill an important gap in the literature about what criteria, processes, and parameters of success Board members and senior managers would use to set priorities fairly

What do hospital decision-makers in Ontario, Canada, have to say about the fairness of priority setting in their institutions?

BACKGROUND: Priority setting, also known as rationing or resource allocation, occurs at all levels of every health care system. Daniels and Sabin have proposed a framework for priority setting in health care institutions called 'accountability for reasonableness', which links priority setting to theories of democratic deliberation. Fairness is a key goal of priority setting. According to 'accountability for reasonableness', health care institutions engaged in priority setting have a claim to fairness if they satisfy four conditions of relevance, publicity, appeals/revision, and enforcement. This is the first study which has surveyed the views of hospital decision makers throughout an entire health system about the fairness of priority setting in their institutions. The purpose of this study is to elicit hospital decision-makers' self-report of the fairness of priority setting in their hospitals using an explicit conceptual framework, 'accountability for reasonableness'. METHODS: 160 Ontario hospital Chief Executive Officers, or their designates, were asked to complete a survey questionnaire concerning priority setting in their publicly funded institutions. Eight-six Ontario hospitals completed this survey, for a response rate of 54%. Six close-ended rating scale questions (e.g. Overall, how fair is priority setting at your hospital?), and 3 open-ended questions (e.g. What do you see as the goal(s) of priority setting in your hospital?) were used. RESULTS: Overall, 60.7% of respondents indicated their hospitals' priority setting was fair. With respect to the 'accountability for reasonableness' conditions, respondents indicated their hospitals performed best for the relevance (75.0%) condition, followed by appeals/revision (56.6%), publicity (56.0%), and enforcement (39.5%). CONCLUSIONS: For the first time hospital Chief Executive Officers within an entire health system were surveyed about the fairness of priority setting practices in their institutions using the conceptual framework 'accountability for reasonableness'. Although many hospital CEOs felt that their priority setting was fair, ample room for improvement was noted, especially for the enforcement condition

The Green Bank Ammonia Survey (GAS): First Results of NH3 mapping the Gould Belt

We present an overview of the first data release (DR1) and first-look science from the Green Bank Ammonia Survey (GAS). GAS is a Large Program at the Green Bank Telescope to map all Gould Belt star-forming regions with $A_V \gtrsim 7$ mag visible from the northern hemisphere in emission from NH$_3$ and other key molecular tracers. This first release includes the data for four regions in Gould Belt clouds: B18 in Taurus, NGC 1333 in Perseus, L1688 in Ophiuchus, and Orion A North in Orion. We compare the NH$_3$ emission to dust continuum emission from Herschel, and find that the two tracers correspond closely. NH$_3$ is present in over 60\% of lines-of-sight with $A_V \gtrsim 7$ mag in three of the four DR1 regions, in agreement with expectations from previous observations. The sole exception is B18, where NH$_3$ is detected toward ~ 40\% of lines-of-sight with $A_V \gtrsim 7$ mag. Moreover, we find that the NH$_3$ emission is generally extended beyond the typical 0.1 pc length scales of dense cores. We produce maps of the gas kinematics, temperature, and NH$_3$ column densities through forward modeling of the hyperfine structure of the NH$_3$ (1,1) and (2,2) lines. We show that the NH$_3$ velocity dispersion, ${\sigma}_v$, and gas kinetic temperature, $T_K$, vary systematically between the regions included in this release, with an increase in both the mean value and spread of ${\sigma}_v$ and $T_K$ with increasing star formation activity. The data presented in this paper are publicly available.Comment: 33 pages, 27 figures, accepted to ApJS. Datasets are publicly available: https://dataverse.harvard.edu/dataverse/GAS_DR

Droplets I: Pressure-Dominated Sub-0.1 pc Coherent Structures in L1688 and B18

We present the observation and analysis of newly discovered coherent structures in the L1688 region of Ophiuchus and the B18 region of Taurus. Using data from the Green Bank Ammonia Survey (GAS), we identify regions of high density and near-constant, almost-thermal, velocity dispersion. Eighteen coherent structures are revealed, twelve in L1688 and six in B18, each of which shows a sharp "transition to coherence" in velocity dispersion around its periphery. The identification of these structures provides a chance to study the coherent structures in molecular clouds statistically. The identified coherent structures have a typical radius of 0.04 pc and a typical mass of 0.4 Msun, generally smaller than previously known coherent cores identified by Goodman et al. (1998), Caselli et al. (2002), and Pineda et al. (2010). We call these structures "droplets." We find that unlike previously known coherent cores, these structures are not virially bound by self-gravity and are instead predominantly confined by ambient pressure. The droplets have density profiles shallower than a critical Bonnor-Ebert sphere, and they have a velocity (VLSR) distribution consistent with the dense gas motions traced by NH3 emission. These results point to a potential formation mechanism through pressure compression and turbulent processes in the dense gas. We present a comparison with a magnetohydrodynamic simulation of a star-forming region, and we speculate on the relationship of droplets with larger, gravitationally bound coherent cores, as well as on the role that droplets and other coherent structures play in the star formation process.Comment: Accepted by ApJ in April, 201