Ethanol reversal of tolerance to the respiratory depressant effects of morphine

Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO(2) in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths

Deuteron and antideuteron production in Au+Au collisions at sqrt(s_NN)=200 GeV

The production of deuterons and antideuterons in the transverse momentum range 1.1 < p_T < 4.3 GeV/c at mid-rapidity in Au + Au collisions at sqrt(s_NN)=200 GeV has been studied by the PHENIX experiment at RHIC. A coalescence analysis comparing the deuteron and antideuteron spectra with those of protons and antiprotons, has been performed. The coalescence probability is equal for both deuterons and antideuterons and increases as a function of p_T, which is consistent with an expanding collision zone. Comparing (anti)proton yields p_bar/p = 0.73 +/- 0.01, with (anti)deuteron yields: d_bar/d = 0.47 +/- 0.03, we estimate that n_bar/n = 0.64 +/- 0.04.Comment: 326 authors, 6 pages text, 5 figures, 1 Table. Submitted to PRL. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Single Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s) = 200 GeV

The invariant differential cross section for inclusive electron production in p+p collisions at sqrt(s) = 200 GeV has been measured by the PHENIX experiment at the Relativistic Heavy Ion Collider over the transverse momentum range $0.4 <= p_T <= 5.0 GeV/c at midrapidity (eta <= 0.35). The contribution to the inclusive electron spectrum from semileptonic decays of hadrons carrying heavy flavor, i.e. charm quarks or, at high p_T, bottom quarks, is determined via three independent methods. The resulting electron spectrum from heavy flavor decays is compared to recent leading and next-to-leading order perturbative QCD calculations. The total cross section of charm quark-antiquark pair production is determined as sigma_(c c^bar) = 0.92 +/- 0.15 (stat.) +- 0.54 (sys.) mb.Comment: 329 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Effects of the neurogranin variant rs12807809 on thalamocortical morphology in schizophrenia

10.1371/journal.pone.0085603PLoS ONE812-POLN

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Accretion disc winds in tidal disruption events: Ultraviolet spectral lines as orientation indicators

ABSTRACT Some tidal disruption events (TDEs) exhibit blueshifted broad absorption lines (BALs) in their rest-frame ultraviolet (UV) spectra, while others display broad emission lines (BELs). Similar phenomenology is observed in quasars and accreting white dwarfs, where it can be interpreted as an orientation effect associated with line formation in an accretion disc wind. We propose and explore a similar unification scheme for TDEs. We present synthetic UV spectra for disc and wind-hosting TDEs, produced by a state-of-the-art Monte Carlo ionization and radiative transfer code. Our models cover a wide range of disc wind geometries and kinematics. Such winds naturally reproduce both BALs and BELs. In general, sightlines looking into the wind cone preferentially produce BALs, while other orientations preferentially produce BELs. We also study the effect of wind clumping and CNO-processed abundances on the observed spectra. Clumpy winds tend to produce stronger UV emission and absorption lines, because clumping increases both the emission measure and the abundances of the relevant ionic species, the latter by reducing the ionization state of the outflow. The main effect of adopting CNO-processed abundances is a weakening of C iv 1550 Å  and an enhancement of N v 1240 Å  in the spectra. We conclude that line formation in an accretion disc wind is a promising mechanism for explaining the diverse UV spectra of TDEs. If this is correct, the relative number of BAL and BEL TDEs can be used to estimate the covering factor of the outflow. The models in this work are publicly available online and upon request.</jats:p

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Criança, violência e saúde: desafios e questões atuais

This paper examines challenges and current issues involved in measuring exposure to different types of violence which are associated mental health problems in children and adolescents. Standardized measures suitable for epidemiological studies, selected based on their relevance in the current literature, are briefly described and commented. The assessment of child's exposure to violence may focus on a specific event (e.g., kidnapping), a specific context (e.g., war) or even of a certain type of exposure (e.g., intrafamilial physical violence). The assessment of child mental health after exposure to violence has traditionally focused on posttraumatic stress disorder (PTSD) - most frequently measured through non-diagnostic scales. However, other mental health reactions may be present and screening as well as diagnostic instruments which may be used to assess these reactions are also described. Two issues of emerging importance - the assessment of impairment and of traumatic grief in children - are also presented. Availability of culturally appropriate instruments is a crucial step towards proper identification of child mental health problems after exposure to violence.Este artigo examina os desafios e perspectivas atuais envolvidos na mensuração da exposição a diferentes tipos de violência e problemas de saúde mental em crianças e adolescentes. Instrumentos padronizados apropriados para estudos epidemiológicos, selecionados com base em sua relevância na literatura, são brevemente descritos e comentados. A avaliação de exposição à violência em crianças pode dizer respeito a um evento específico (como sequestro) ou um contexto específico (como guerra) ou mesmo um determinado tipo de exposição (como violência física intrafamiliar). A avaliação da saúde mental infantil após a exposição à violência tradicionalmente concentrou-se na avaliação do transtorno de estresse pós-traumático (TEPT) - freqüentemente avaliado através de escalas não-diagnósticas. Porém, outras reações psicológicas podem ocorrer e instrumentos que podem ser usados para avaliar estas reações também são descritos neste artigo. Dois tópicos de importância emergente - a avaliação de prejuízo funcional e do pesar traumático em crianças - são também apresentados. Instrumentos culturalmente apropriados são essenciais para a identificação de problemas de saúde mental em crianças após a exposição à violência.Division of Child and Adolescent PsychiatryUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Departamento de PsiquiatriaUNIFESP, EPM, Depto. de PsiquiatriaSciEL

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure