The placebo effect: from concepts to genes

Despite its initial treatment as a nuisance variable, the placebo effect is now recognized as a powerful determinant of health across many different diseases and encounters. This is in light of some remarkable findings ranging from demonstrations that the placebo effect significantly modulates the response to active treatments in conditions such as pain, anxiety, Parkinson’s disease, and some surgical procedures. Here, we review pioneering studies and recent advances in behavioural, neurobiological, and genetic influences on the placebo effect. Based on a previous developed conceptual framework, the placebo effect is presented as the product of a general expectancy learning mechanism in which verbal, conditioned, observational, and social cues are centrally integrated to change behaviours and outcomes. Examples of the integration of verbal and conditioned cues, such as instructed reversal of placebo effects are also incorporated into this model. We discuss neuroimaging studies that using well-established behavioral paradigms have identified key brain regions and modulatory mechanisms underlying placebo effects. Finally, we present a synthesis of recent genetics studies on the placebo effect, highlighting a promising link between genetic variants in the dopamine, opioid, serotonin, and endocannabinoid pathways and placebo responsiveness. Greater understanding of the behavioural, neurobiological, and genetic influences on the placebo effect is critical for evaluating medical interventions and may allow health professionals to tailor and personalize interventions in order to maximise treatment outcomes in clinical settings

The placebo effect: from concepts to genes

Despite its initial treatment as a nuisance variable, the placebo effect is now recognized as a powerful determinant of health across many different diseases and encounters. This is in light of some remarkable findings ranging from demonstrations that the placebo effect significantly modulates the response to active treatments in conditions such as pain, anxiety, Parkinson’s disease, and some surgical procedures. Here, we review pioneering studies and recent advances in behavioural, neurobiological, and genetic influences on the placebo effect. Based on a previous developed conceptual framework, the placebo effect is presented as the product of a general expectancy learning mechanism in which verbal, conditioned, observational, and social cues are centrally integrated to change behaviours and outcomes. Examples of the integration of verbal and conditioned cues, such as instructed reversal of placebo effects are also incorporated into this model. We discuss neuroimaging studies that using well-established behavioral paradigms have identified key brain regions and modulatory mechanisms underlying placebo effects. Finally, we present a synthesis of recent genetics studies on the placebo effect, highlighting a promising link between genetic variants in the dopamine, opioid, serotonin, and endocannabinoid pathways and placebo responsiveness. Greater understanding of the behavioural, neurobiological, and genetic influences on the placebo effect is critical for evaluating medical interventions and may allow health professionals to tailor and personalize interventions in order to maximise treatment outcomes in clinical settings

The Reliability of Foot and Ankle Bone and Joint Kinematics Measured With Biplanar Videoradiography and Manual Scientific Rotoscoping

The intricate motion of the small bones of the feet are critical for its diverse function. Accurately measuring the 3-dimensional (3D) motion of these bones has attracted much attention over the years and until recently, was limited to invasive techniques or quantification of functional segments using multi-segment foot models. Biplanar videoradiography and model-based scientific rotoscoping offers an exciting alternative that allows us to focus on the intricate motion of individual bones in the foot. However, scientific rotoscoping, the process of rotating and translating a 3D bone model so that it aligns with the captured x-ray images, is either semi- or completely manual and it is unknown how much human error affects tracking results. Thus, the aim of this study was to quantify the inter- and intra-operator reliability of manually rotoscoping in vivo bone motion of the tibia, talus, and calcaneus during running. Three-dimensional CT bone volumes and high-speed biplanar videoradiography images of the foot were acquired on six participants. The six-degree-of-freedom motions of the tibia, talus, and calcaneus were determined using a manual markerless registration algorithm. Two operators performed the tracking, and additionally, the first operator re-tracked all bones, to test for intra-operator effects. Mean RMS errors were 1.86 mm and 1.90° for intra-operator comparisons and 2.30 mm and 2.60° for inter-operator comparisons across all bones and planes. The moderate to strong similarity values indicate that tracking bones and joint kinematics between sessions and operators is reliable for running. These errors are likely acceptable for defining gross joint angles. However, this magnitude of error may limit the capacity to perform advanced analyses of joint interactions, particularly those that require precise (sub-millimeter) estimates of bone position and orientation. Optimizing the view and image quality of the biplanar videoradiography system as well as the automated tracking algorithms for rotoscoping bones in the foot are required to reduce these errors and the time burden associated with the manual processing

ISO LWS Spectroscopy of M82: A Unified Evolutionary Model

We present the first complete far-infrared spectrum (43 to 197 um) of M82, the brightest infrared galaxy in the sky, taken with the Long Wavelength Spectrometer of the Infrared Space Observatory (ISO). We detected seven fine structure emission lines, [OI] 63 and 145 um, [OIII] 52 and 88 um, [NII] 122 um, [NIII] 57 um and [CII] 158 um, and fit their ratios to a combination starburst and photo-dissociation region (PDR) model. The best fit is obtained with HII regions with n = 250 cm^{-3} and an ionization parameter of 10^{-3.5} and PDRs with n = 10^{3.3} cm^{-3} and a far-ultraviolet flux of G_o = 10^{2.8}. We applied both continuous and instantaneous starburst models, with our best fit being a 3-5 Myr old instantaneous burst model with a 100 M_o cut-off. We also detected the ground state rotational line of OH in absorption at 119.4 um. No excited level OH transitions are apparent, indicating that the OH is almost entirely in its ground state with a column density ~ 4x10^{14} cm^{-2}. The spectral energy distribution over the LWS wavelength range is well fit with a 48 K dust temperature and an optical depth, tau_{Dust} proportional to lambda^{-1}.Comment: 23 pages, 4 figures, accepted by ApJ, Feb. 1, 199

ENSO’s impact on the gap wind regions of the eastern tropical Pacific Ocean

Author Posting. © American Meteorological Society, 2012. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 25 (2012): 3549–3565, doi:10.1175/JCLI-D-11-00320.1.The recently released NCEP Climate Forecast System Reanalysis (CFSR) is used to examine the response to ENSO in the northeast tropical Pacific Ocean (NETP) during 1979–2009. The normally cool Pacific sea surface temperatures (SSTs) associated with wind jets through the gaps in the Central American mountains at Tehuantepec, Papagayo, and Panama are substantially warmer (colder) than the surrounding ocean during El Niño (La Niña) events. Ocean dynamics generate the ENSO-related SST anomalies in the gap wind regions as the surface fluxes damp the SSTs anomalies, while the Ekman heat transport is generally in quadrature with the anomalies. The ENSO-driven warming is associated with large-scale deepening of the thermocline; with the cold thermocline water at greater depths during El Niño in the NETP, it is less likely to be vertically mixed to the surface, particularly in the gap wind regions where the thermocline is normally very close to the surface. The thermocline deepening is enhanced to the south of the Costa Rica Dome in the Papagayo region, which contributes to the local ENSO-driven SST anomalies. The NETP thermocline changes are due to coastal Kelvin waves that initiate westward-propagating Rossby waves, and possibly ocean eddies, rather than by local Ekman pumping. These findings were confirmed with regional ocean model experiments: only integrations that included interannually varying ocean boundary conditions were able to simulate the thermocline deepening and localized warming in the NETP during El Niño events; the simulation with variable surface fluxes, but boundary conditions that repeated the seasonal cycle, did not.This research was supported by grants from the NOAA office of Global Programs and the NSF Climate and Global Dynamics Division.2012-11-1

Multi-wavelength spectroscopy of the bipolar outflow from Cepheus E

Cepheus E is the site of an exceptional example of a protostellar outflow with a very young dynamical age and extremely high near infrared luminosity. We combine molecular spectroscopic data from the submillimeter to the near infrared in order to interpret the rotational excitation of CO and the ro-vibrational excitation of H2. We conclude that C-type shocks with a paraboloidal bow shock geometry can simultaneously explain all the molecular excitations. Extinction accounts for the deviation of the column densities from local thermodynamic equilibrium. A difference in the extinction between the red and blue-shifted outflow lobes may account for the measured flux difference. The outflow is deeply embedded in a clump of density 10^5cm^-3, yet a good fraction of atomic hydrogen, about 40%, is required to explain the excitation and statistical equilibrium. We propose that this atomic component arises, self-consistently, from the dissociated gas at the apex of the leading bow shocks and the relatively long molecule reformation time. At least 20 bow shocks are required in each lobe, although these may be sub-divided into smaller bows and turbulent shocked regions. The total outflow mechanical power and cooling amounts to over 30L_\odot, almost half the source's bolometric luminosity. Nevertheless, only about 6% of the clump mass has been set in outward motion by the outflow, allowing a collapse to continue.Comment: 14 pages, 8 figures, accepted for publication in Ap