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The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland – CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.
Medical residents are an important group for antimicrobial stewardship programs (ASPs) to target with interventions aimed at improving antibiotic prescribing. In this study, we compared antimicrobial prescribing practices of 2 academic medical teams receiving different ASP training approaches along with a hospitalist control group.
Retrospective cohort study comparing guideline-concordant antibiotic prescribing for 3 common infections among a family medicine (FM) resident service, an internal medicine (IM) resident service, and hospitalists.
Community teaching hospital.
Adult patients admitted between July 1, 2016, and June 30, 2017, with a discharge diagnosis of pneumonia, cellulitis, and urinary tract infections were reviewed.
All 3 medical teams received identical baseline ASP education and daily antibiotic prescribing audit with feedback via clinical pharmacists. The FM resident service received an additional layer of targeted ASP intervention that included biweekly stewardship-focused rounds with an ASP physician and clinical pharmacist leadership. Guideline-concordant prescribing was assessed based on the institution’s ASP guidelines.
Of 1,572 patients, 295 (18.8%) were eligible for inclusion (FM, 96; IM, 69; hospitalist, 130). The percentage of patients receiving guideline-concordant antibiotic selection empirically was similar between groups for all diagnoses (FM, 87.5%; IM, 87%; hospitalist, 83.8%; P = .702). No differences were observed in appropriate definitive antibiotic selection among groups (FM, 92.4%; IM, 89.1%; hospitalist, 89.9%; P = .746). The FM resident service was more likely to prescribe a guideline-concordant duration of therapy across all diagnoses (FM, 74%; IM, 56.5%; hospitalist, 44.6%; P < .001).
Adding dedicated stewardship-focused rounds into the graduate medical curriculum demonstrated increased guideline adherence specifically to duration of therapy recommendations.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
Several programs in the NCI nanotech seek to develop unique platforms for targeted drug delivery. These platforms involve the use of nanometer-sized macromolecules and nanoparticles. Requirements should include a diameter small enough that the drug and carrier will escape the blood stream through vascular pores and then specifically target cells within tumors or selected organs. Importantly, these platforms should also internalize within a cell and localize to intracellular structures. Achieving proof of concept with these technologies would then require additional funding from venture capital or private corporate investment to support human clinical trials. Given the activity of nanoparticles for drug, this technology has the potential to revolutionize therapeutics and provide unique solutions for all aspects of cancer care. The potential risks, benefits and technical requirements for these platforms will be reviewed. Different technologies will be compared and contrasted for the ability to meet the need of cancer therapeutics.
Chemically defended benthic macroalgae that dominate shallow, hard bottom communities along the western Antarctic Peninsula support very high densities of mesograzers, particularly amphipods but also small gastropods. Previous studies have demonstrated that the macroalgae and amphipods form a mutualistic relationship. The chemically defended macroalgae provide the amphipods with a refuge from predation while the macroalgae benefit from the amphipods greatly reducing surface fouling by smaller algae. One of the three most important macroalgae in terms of overstory cover, Himantothallus grandifolius, forms huge blades that can carpet the benthos. Field observations suggest that gastropods may be higher in relative abundance in proportion to amphipods on H. grandifolius than on other overstory macroalgae. The present study documents the finding that natural abundances of gastropods on H. grandifolius maintained in mesocosms reduce fouling by microscopic algae, primarily diatoms. However, amphipods are probably also important in keeping the macroalga clean of diatoms in nature. In a smaller scale experiment, three gastropod species were differentially effective at reducing diatom coverage on H. grandifolius. The hypothesis that gastropods benefit from associating with H. grandifolius in potentially gaining a refuge from sea-star predation was also tested but not supported by the experimental results.
We experimentally investigate the two-phase interplay in an open-channel turbulent boundary layer laden with finite-size particles at global volume fractions between 4 and 25 %. The working fluid (water) and the dispersed phase (hydrogel spheres) have closely matched refractive indices, allowing us to measure the properties of both phases using particle image velocimetry and particle tracking velocimetry, respectively. The particles have a diameter of approximately 9 % of the channel depth and are slightly denser than the fluid. The negative buoyancy causes a strong vertical concentration gradient, characterized by discrete and closely spaced particle layers parallel to the wall. Even at the lowest considered volume fractions, the near-wall fluid velocity and velocity gradients are strongly reduced, with large mean shear throughout most of the channel height. This indicates that the local effective viscosity of the suspension is greatly increased due to the friction between particle layers sliding over one another. The particles consistently lag the fluid and leave their footprint on its mean and fluctuating velocity profiles. The turbulent activity is damped near the wall, where the nearly packed particles disrupt and suppress large-scale turbulent fluctuations and redistribute some of the kinetic energy to smaller scales. On the other hand, in the outer region of the flow where the local particle concentration is low, the mean shear produces strong Reynolds stresses, with enhanced sweeps and ejections and frequent swirling events.
This paper presents a review of the current status of photodiode array systems adapted for Energy Dispersive EXAFS (EDE) using a synchrotron radiation source. The performance of a conventional Reticon PDA is compared with that of a hybrid CCD. The specification of a new detector system for EDE is discussed in the light of experience gained with current linear detectors.
The Rietveld profile refinement method is probably the most popular technique used for the crystallographic characterization of materials including crystal structures and phase analysis, but it has been used mostly with ideal powder sample, not with textured polycrystals, because effects of strong and complex textures. Most technological materials are fabricated by using thermo-mechanical forming processes, which inevitably produce strong and complex preferential orientations of the crystallites. Consequently, the diffraction patterns of a given technological material are not unique but vary considerably with the measuring direction, with intensity variations as large as factors of hundreds, depending on the degree of texture. The texture effect on the diffraction pattern of a certain sample direction is directly proportional to the pole density of the corresponding inverse pole figure, which can be obtained from the three-dimensional orientation distribution function (ODF) of the material. The ODFs of materials with high crystal symmetry, such as cubic, hexagonal, tetragonal, and orthorhombic, can be determined quite precisely, using modern texture analysis techniques (for example, Bungel, Wenk, and Kallend et al.). The pole density distributions of the inverse pole figures can be used in the diffraction profile calculation of a highly textured sample.
X-ray diffraction angles are measured precisely, conveniently, and automatically by a specially designed instrument, the automatic precision X-ray goniometer connected on line to an Elliott 903B data processor. A monitor program controls two such instruments and two diffractometers simultaneously and allows a comprehensive set of experiments to be performed. The sensitivity is such that, when translated into terms of changes in the crystal-lattice parameter, a precision of 1 part in 10,000,000 is being attained, and indications are that absolute measurements are almost as good. The procedures, instrument, and automatic control are described, and the results of performance tests and some applications are given.
We study experimentally the spatial distribution, settling and interaction of sub-Kolmogorov inertial particles with homogeneous turbulence. Utilizing a zero-mean-flow air turbulence chamber, we drop size-selected solid particles and study their dynamics with particle imaging and tracking velocimetry at multiple resolutions. The carrier flow is simultaneously measured by particle image velocimetry of suspended tracers, allowing the characterization of the interplay between both the dispersed and continuous phases. The turbulence Reynolds number based on the Taylor microscale ranges from
, while the particle Stokes number based on the Kolmogorov scale varies between
. Clustering is confirmed to be most intense for
, but it extends over larger scales for heavier particles. Individual clusters form a hierarchy of self-similar, fractal-like objects, preferentially aligned with gravity and with sizes that can reach the integral scale of the turbulence. Remarkably, the settling velocity of
particles can be several times larger than the still-air terminal velocity, and the clusters can fall even faster. This is caused by downward fluid fluctuations preferentially sweeping the particles, and we propose that this mechanism is influenced by both large and small scales of the turbulence. The particle–fluid slip velocities show large variance, and both the instantaneous particle Reynolds number and drag coefficient can greatly differ from their nominal values. Finally, for sufficient loadings, the particles generally augment the small-scale fluid velocity fluctuations, which however may account for a limited fraction of the turbulent kinetic energy.
To report functional recovery, symptomatic remission, and sustained symptomatic remission rates after treatment with aripiprazole once-monthly 400mg (AOM 400) administered every 4weeks for up to 52weeks as maintenance treatment in a mixed cohort of AOM 400 naïve (de novo) and experienced adults (rollover) with bipolar I disorder (BP-I).
This open-label study (NCT01710709) enrolled de novo patients with a diagnosis of BP-I and ≥1 previous manic or mixed episode and rollover patients who completed a randomized, double-blind, placebo-controlled study assessing the efficacy and safety of AOM 400 (NCT01567527). Efficacy was assessed by mean changes from baseline in Young-Mania Rating Scale (YMRS), Montgomery-Asberg Depressive Rating Scale (MADRS), and Clinical Global Impression- Bipolar Version-Severity of Illness (CGI-BP-S) scores. Sustained functional recovery was defined as a total score of ≤11 on the Functioning Assessment Short Test (FAST) for ≥8 consecutive weeks. Remission was defined as YMRS and MADRS total scores ≤12, and sustained remission was defined as meeting criteria for remission for 8 consecutive weeks. The study included a screening phase (6weeks) for de novo patients, an oral aripiprazole conversion phase (4–6weeks), an oral stabilization phase (4–12weeks), and an AOM 400 maintenance phase (up to 52weeks). Rollover patients entered directly into the AOM 400 maintenance phase.
A total of 464 subjects entered the maintenance phase and 63% (291/464) completed the trial. Of patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. The most frequent reasons for discontinuation were withdrawal of consent (11%) and adverse events (AEs) (10%). Weight increase (1.5%, 7/464) and BP-I (0.9%, 4/464) were the most common reasons for discontinuation due to AEs. Improvements in mean YMRS, MADRS, CGI-BP-S, and FAST scores achieved in previous phases were maintained over 52weeks. Treatment-emergent AEs experienced by >10% of the patients were akathisia (14.7%), weight increased (13.4%), nasopharyngitis (12.1%), and insomnia (11.0%). A high proportion of de novo patients met the criteria for symptomatic remission (87.2%, 328/376) and sustained remission (77%, 292/379) by last visit. Rollover patients’ remission rate remained stable (98.8%, 84/85) by last visit. Of the rollover patients, 35/85 (43%) and 35/116 (36%) of de novo subjects met the criteria for sustained functional recovery after study completion.
Patients treated with AOM 400 maintained symptomatic and functional stability for up to 52weeks. Importantly, more than one-third of patients achieved sustained functional recovery using a strict criterion. Overall, AOM 400 was safe and well tolerated in patients with BP-I. Results support AOM 400 as a viable once-monthlyoption for maintenance treatment of BP-I.
These data were previously presented at the 31st ECNP Congress, 2018, Barcelona,Spain.
Funding Acknowledgements: The study was supported by Otsuka Pharmaceutical Development & Commercialization, Inc.
Most current models of nonnative speech perception (e.g., extended perceptual assimilation model, PAM-L2, Best & Tyler, 2007; speech learning model, Flege, 1995; native language magnet model, Kuhl, 1993) base their predictions on the native/nonnative status of individual phonetic/phonological segments. This paper demonstrates that the phonotactic properties of Japanese influence the perception of natively contrasting consonants and suggests that phonotactic influence must be formally incorporated in these models. We first propose that by extending the perceptual categories outlined in PAM-L2 to incorporate sequences of sounds, we can account for the effects of differences in native and nonnative phonotactics on nonnative and cross-language segmental perception. In addition, we test predictions based on such an extension in two perceptual experiments. In Experiment 1, Japanese listeners categorized and rated vowel–consonant–vowel strings in combinations that either obeyed or violated Japanese phonotactics. The participants categorized phonotactically illegal strings to the perceptually nearest (legal) categories. In Experiment 2, participants discriminated the same strings in AXB discrimination tests. Our results show that Japanese listeners are more accurate and have faster response times when discriminating between legal strings than between legal and illegal strings. These findings expose serious shortcomings in currently accepted nonnative perception models, which offer no framework for the influence of native language phonotactics.
Various paleoclimatic records have been used to reconstruct the hydrologic history of the Altiplano, relating this history to past variability of the South American summer monsoon. Prior studies of the southern Altiplano, the location of the world’s largest salt flat, the Salar de Uyuni, and its neighbor, the Salar de Coipasa, generally agree in their reconstructions of the climate history of the past ∼24 ka. Some studies, however, have highly divergent climatic records and interpretations of earlier periods. In this study, lake-level variation was reconstructed from a ∼14-m-long sediment core from the Salar de Coipasa. These sediments span the last ∼40 ka. Lacustrine sediment accumulation was apparently continuous in the basin from ∼40 to 6 ka, with dry or very shallow conditions afterward. The fossil diatom stratigraphy and geochemical data (δ13C, δ15N, %Ca, C/N) indicate fluctuations in lake level from shallow to moderately deep, with the deepest conditions correlative with the Heinrich-1 and Younger Dryas events. The stratigraphy shows a continuous lake of variable depth and salinity during the last glacial maximum and latter stages of Marine Oxygen Isotope Stage 3 and is consistent with environmental inferences and the original chronology of a drill core from Salar de Uyuni.
The effect of small noise in a smooth dynamical system is negligible on any finite time interval; in this paper we study situations where the effect persists on intervals increasing to ∞. Such an asymptotic regime occurs when the system starts from an initial condition that is sufficiently close to an unstable fixed point. In this case, under appropriate scaling, the trajectory converges to a solution of the unperturbed system started from a certain random initial condition. In this paper we consider the case of one-dimensional diffusions on the positive half-line; this case often arises as a scaling limit in population dynamics.