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Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).
Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.
Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.
This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
Turbulence is commonly observed in nearly collisionless heliospheric plasmas, including the solar wind and corona and the Earth’s magnetosphere. Understanding the collisionless mechanisms responsible for the energy transfer from the turbulent fluctuations to the particles is a frontier in kinetic turbulence research. Collisionless energy transfer from the turbulence to the particles can take place reversibly, resulting in non-thermal energy in the particle velocity distribution functions (VDFs) before eventual collisional thermalization is realized. Exploiting the information contained in the fluctuations in the VDFs is valuable. Here we apply a recently developed method based on VDFs, the field–particle correlation technique, to a
, solar-wind-like, low-frequency Alfvénic turbulence simulation with well-resolved phase space to identify the field–particle energy transfer in velocity space. The field–particle correlations reveal that the energy transfer, mediated by the parallel electric field, results in significant structuring of the VDF in the direction parallel to the magnetic field. Fourier modes representing the length scales between the ion and electron gyroradii show that energy transfer is resonant in nature, localized in velocity space to the Landau resonances for each Fourier mode. The energy transfer closely follows the Landau resonant velocities with varying perpendicular wavenumber
. This resonant signature, consistent with Landau damping, is observed in all diagnosed Fourier modes that cover the dissipation range of the simulation.
We investigated strain relaxation in (001) InGaAs/GaAs structures using both double and triple axis high resolution x-ray diffraction techniques. We determined diat broadening which is observed in double axis scans stews pnmanly from mosaic spread and not from lattice constant variations in the layer, demonstrating that relaxation is uniform along the growth direction. These observations held for layers with both low and high indium content and extents of relaxation. Triple axis measurements showed that the peak broadening was due exclusively to mosaic spread for the low indium content samples and also confirmed earlier double axis measurements that a crystallographic tilt of the epitaxial layer was attributed to substrate miscut. The ability to distinguish the source of peak broadening and crystallographic tilts makes triple axis diffraction a powerful characterization technique for the study of mismatched epitaxial layers.
Both double-crystal and triple-axis x-ray diffraction techniques have been used to study complex SiGe/Si structures. A novel method for measuring the nucleation activation energy of dislocations in strain relaxed SiGe/Si structures is presented to illustrate the usefulness of these techniques.
We report the utility of whole-genome sequencing (WGS) conducted in a clinically relevant time frame (ie, sufficient for guiding management decision), in managing a Streptococcus pyogenes outbreak, and present a comparison of its performance with emm typing.
A 2,000-bed tertiary-care psychiatric hospital.
Active surveillance was conducted to identify new cases of S. pyogenes. WGS guided targeted epidemiological investigations, and infection control measures were implemented. Single-nucleotide polymorphism (SNP)–based genome phylogeny, emm typing, and multilocus sequence typing (MLST) were performed. We compared the ability of WGS and emm typing to correctly identify person-to-person transmission and to guide the management of the outbreak.
The study included 204 patients and 152 staff. We identified 35 patients and 2 staff members with S. pyogenes. WGS revealed polyclonal S. pyogenes infections with 3 genetically distinct phylogenetic clusters (C1–C3). Cluster C1 isolates were all emm type 4, sequence type 915 and had pairwise SNP differences of 0–5, which suggested recent person-to-person transmissions. Epidemiological investigation revealed that cluster C1 was mediated by dermal colonization and transmission of S. pyogenes in a male residential ward. Clusters C2 and C3 were genomically diverse, with pairwise SNP differences of 21–45 and 26–58, and emm 11 and mostly emm120, respectively. Clusters C2 and C3, which may have been considered person-to-person transmissions by emm typing, were shown by WGS to be unlikely by integrating pairwise SNP differences with epidemiology.
WGS had higher resolution than emm typing in identifying clusters with recent and ongoing person-to-person transmissions, which allowed implementation of targeted intervention to control the outbreak.
Piglets are characteristically cold intolerant and thus susceptible to high mortality. However, browning of white adipose tissue (WAT) can induce non-shivering thermogenesis as a potential strategy to facilitate the animal’s response to cold. Whether cold exposure can induce browning of subcutaneous WAT (sWAT) in piglets in a similar manner as it can in humans remains largely unknown. In this study, piglets were exposed to acute cold (4°C, 10 h) or chronic cold exposure (8°C, 15 days), and the genes and proteins of uncoupling protein 1 (UCP1)-dependent and independent thermogenesis, mitochondrial biogenesis, lipogenic and lipolytic processes were analysed. Interestingly, acute cold exposure induced browning of porcine sWAT, smaller adipocytes and the upregulated expression of UCP1, PGC1α, PGC1β, C/EBPβ, Cidea, UCP3, CKMT1 and PM20D1. Conversely, chronic cold exposure impaired the browning process, reduced mitochondrial numbers and the expression of browning markers, including UCP1, PGC1α and PRDM16. The present study demonstrated that acute cold exposure (but not chronic cold exposure) induces porcine sWAT browning. Thus, browning of porcine sWAT could be a novel strategy to balance the body temperature of piglets, and thus could be protective against cold exposure.
Young Type Ia supernova remnants (SNRs) are characterized by Balmer-dominated optical spectra, well-defined shell morphologies, > 1036 ergs s−1 X-ray luminosities, and a lack of massive stars and dense interstellar gas in their vicinity. Applying these characteristics and using archival deep HST and Chandra observations of M83, we search for young Type Ia SNRs in this spiral galaxy. This is a very difficult task!
Supernovae (SNe) explode in environments that have been significantly modified by the SN progenitors. For core-collapse SNe, the massive progenitors ionize the ambient interstellar medium (ISM) via UV radiation and sweep the ambient ISM via fast stellar winds during the main sequence phase, replenish the surroundings with stellar material via slow winds during the luminous blue variable (LBV) or red supergiant (RSG) phase, and sweep up the circumstellar medium (CSM) via fast winds during the Wolf-Rayet (WR) phase. If a massive progenitor was in a close binary system, the binary interaction could have caused mass ejection in certain preferred directions, such as the orbital plane, and even bipolar outflow/jet. As a massive star finally explodes, the SN ejecta interacts first with the CSM that was ejected and shaped by the star itself. As the newly formed supernova remnant (SNR) expands further, it encounters interstellar structures that were shaped by the progenitor from earlier times. Therefore, the structure and evolution of a SNR is largely dependent on the initial mass and close binarity of the SN progenitor. The Large Magellanic Cloud (LMC) has an excellent sample of over 50 confirmed SNRs that are well resolved by Hubble Space Telescope, Chandra X-ray Observatory, and Spitzer Space Telescope. These multi-wavelength observations allow us to conduct stellar forensics in SNRs and understand the wide variety of morphologies and physical properties of SNRs observed.
Turbulence plays a key role in the conversion of the energy of large-scale fields and flows to plasma heat, impacting the macroscopic evolution of the heliosphere and other astrophysical plasma systems. Although we have long been able to make direct spacecraft measurements of all aspects of the electromagnetic field and plasma fluctuations in near-Earth space, our understanding of the physical mechanisms responsible for the damping of the turbulent fluctuations in heliospheric plasmas remains incomplete. Here we propose an innovative field–particle correlation technique that can be used to measure directly the secular energy transfer from fields to particles associated with collisionless damping of the turbulent fluctuations. Furthermore, this novel procedure yields information about the collisionless energy transfer as a function of particle velocity, providing vital new information that can help to identify the dominant collisionless mechanism governing the damping of the turbulent fluctuations. Kinetic plasma theory is used to devise the appropriate correlation to diagnose Landau damping, and the field–particle correlation technique is thoroughly illustrated using the simplified case of the Landau damping of Langmuir waves in a 1D-1V (one dimension in physical space and one dimension in velocity space) Vlasov–Poisson plasma. Generalizations necessary to apply the field–particle correlation technique to diagnose the collisionless damping of turbulent fluctuations in the solar wind are discussed, highlighting several caveats. This novel field–particle correlation technique is intended to be used as a primary analysis tool for measurements from current, upcoming and proposed spacecraft missions that are focused on the kinetic microphysics of weakly collisional heliospheric plasmas, including the Magnetospheric Multiscale (MMS), Solar Probe Plus, Solar Orbiter and Turbulence Heating ObserveR (THOR) missions.
Recurrent GBM and AA have a dismal prognosis and a high unmet need for effective therapies. Toca 511 (vocimagene amiretrorepvec) is an investigational retroviral replicating vector that encodes the transgene cytosine deaminase (CD). Toca 511 selectively infects, persists and spreads in tumor. Subsequent oral administration of 5-fluorocytosine (Toca FC) produces 5-fluorouracil (5-FU) by CD within infected cells. 5-FU kills cancer cells and myeloid derived suppressor cells, inducing robust antitumor immune responses in animal models. Clinical data from phase 1 trials are consistent with this mechanism of action, and show extended survival compared to historical controls. Toca 5 is a multicenter, randomized, open-label Phase 2/3 trial of Toca 511 and Toca FC versus standard of care administered to patients undergoing resection for first or second recurrence of GBM or AA. Phase 2 will enroll 170 patients. Primary endpoint is overall survival (OS). Key secondary endpoints are safety, objective response rate, clinical benefit rate, progression-free survival, and landmark OS. Key inclusion criteria are age 18-75 years, histologically proven GBM or AA, measurable disease preoperatively of less than 5cm, candidate for equal or greater 80% resection of enhancing tumor based on pre-operative evaluation, and KPS equal or greater to 70. Assays for immune monitoring will be performed and molecular profiling of resected tumor samples will be correlated efficacy.
Recurrent glioblastoma (GBM) has an unmet need for effective therapies. Toca 511 (vocimagene amiretrorepvec), a retroviral replicating vector with the transgene cytosine deaminase, selectively infects, persists and spreads in tumor. Subsequent oral administration of 5-fluorocytosine (Toca FC) produces 5-fluorouracil (5-FU) within infected cells. 5-FU kills cancer cells and myeloid derived suppressor cells, inducing robust antitumor immune responses in animal models. In 2 Phase 1 studies, Toca 511 was administered into the cavity wall after surgical resection (NCT01470794) or intratumoral injection by biopsy needle (NCT01156584). To provide context to the results observed, subjects were compared to an external lomustine treated control (Courtesy Denovo Biopharma; Wick 2010). Treatment with Toca 511/Toca FC from 2 Phase I studies showed significant improvement in OS HR equals to 0.48, p less than 0.001, with similar effect in the surgical resection (OS HR 0.45, p equals to 0.003) and intratumoral injection (OS HR 0.56, p equals to 0.060). Fewer related greater or equal to Grade 3 adverse events (AEs) were reported for Toca 511/Toca FC (2.5 percent) vs. lomustine (36.9 percent). There was a virtual absence of hematologic toxicity for Toca 511/Toca FC vs. lomustine (Grade greater or equal to 3 thrombocytopenia 23.8 percent). Discontinuations for AEs occurred in 0percent for Toca 511/Toca FC vs. 4.8 percent for lomustine. Toca 511 is surgically delivered and treatment-emergent AEs regardless of attribution included incision site pain (20 percent), procedural pain (12.5 percent), and wound infection (5 percent) vs. 0percent, 1.2 percent, 1.2 percent respectively for lomustine. Toca 511/Toca FC significantly improved survival and safety relative to lomustine. A Phase 2/3 trial has launched (NCT02414165).
Cosmology is one of the most dynamically evolving areas of astrophysics today. Twenty years ago the estimates of the amplitude of the primordial fluctuations were about 10-3, almost a factor of 100 off of today’s measurements. Ten years ago we could only hope for high precision measurements of large scale structure, there were less than 5000 redshifts measured, and only a handful of normal galaxies with z > 1 were known. Computer models of structure formation had just begun to consider non-power-law spectra based on physical models like hot/cold dark matter. As a consequence there was considerable freedom in adjusting parameters in the various galaxy formation scenarios. In contrast, many of today’s debates are about factors of 2 and soon we will be arguing about 10% differences. The Harrison-Zeldovich shape of the primordial fluctuation spectrum, first derived from philosophical arguments can now be quantified from detections of fluctuations by COBE. The number of available redshifts is beyond 50,000, and soon we will have redshift surveys surpassing 1 million galaxies. N-body simulations are becoming more sophisticated, of higher resolution, and incorporating complex gas dynamics.
The image of Sk −69° 202 was scanned and analyzed on eight (of 32 available) blue through near-infrared photographic plates obtained at the prime focus of the Cerro Tololo Inter-American Observatory 4-meter telescope during 1974–1983. Both intensity syntheses of the image and density differences were derived by means of reference stars from the same plates, including the similar nearby object Sk −69° 203. Several of the density differences are shown in Figure 1. The analysis shows that the 12m blue supergiant in Sk −69° 202 (Star 1) has two companions with V magnitudes, position angles, and separations 315°, 3″ (Star 2) and 115°, 1.″5 (Star 3), respectively. Both companions appear to be early-type stars; there is no evidence for a bright red star in the system. The two companions are responsible for the spectra observed by the International Ultraviolet Explorer following the decline of the SN in the far UV, so that Star 1 has disappeared and was probably the progenitor. The most likely interpretation is that it was a post-red supergiant evolving blueward in the HR diagram.
Loss of cortical volume in frontotemporal regions occurs in patients with first-episode psychosis (FEP) and longitudinal studies have reported progressive brain volume changes at different stages of the disease, even if cognitive deficits remain stable over time. We investigated cortical changes in patients over the 2 years following their FEP and their associations with clinical and cognitive measures.
Twenty-seven patients after their FEP (20 with schizophrenia, seven with schizo-affective disorder) and 25 healthy controls matched for age and gender participated in this study. Magnetic resonance imaging (MRI) was performed on a 1.5-T scanner both at baseline and after 2 years. Area and thickness of the cortex were measured using surface-based morphometry (SBM). Patients also underwent neuropsychological testing at these two time points.
Progressive cortical thinning in the superior and inferior frontal and, to a lesser extent, superior temporal cortex was observed in patients. Cortical area remained constant. Cortical thinning was associated with duration of treatment at a trend level and was predicted by baseline measures of IQ and working memory. Cortical thinning occurred in the absence of clinical or cognitive deterioration.
The clinical implications of these cortical changes remain uncertain, but patients with less cognitive reserve may be more vulnerable to developing cortical abnormalities when exposed to medication or other disease-related biological factors.
We describe the growth of high quality AlN and GaN on Si(111) by gas source molecular beam epitaxy (GSMBE) with ammonia (NH3). The initial nucleation (at 1130−1190K) of an AlN monolayer with full substrate coverage resulted in a very rapid transition to two-dimensional (2D) growth mode of AlN. The rapid transition to the 2D growth mode of AlN is essential for the subsequent growth of high quality GaN, and complete elimination of cracking in thick ( > 2 μm) GaN layers. We show, using Raman scattering (RS) and photoluminescence (PL) measurements, that the tensile stress in the GaN is due to thermal expansion mismatch, is below the ultimate strength of breaking of GaN, and produces a sizable shift in the bandgap. We show that the GSMBE AlN and GaN layers grown on Si can be used as a substrate for subsequent deposition of thick AlN and GaN layers by hydride vapor phase epitaxy (HVPE).
Mesa and planar geometry GaN Schottky rectifiers were fabricated on 3-12µm thick epitaxial layers. In planar diodes utilizing resistive GaN, a reverse breakdown voltage of 3.1 kV was achieved in structures containing p-guard rings and employing extension of the Schottky contact edge over an oxide layer. In devices without edge termination, the reverse breakdown voltage was 2.3 kV. Mesa diodes fabricated on conducting GaN had breakdown voltages in the range 200-400 V, with on-state resistances as low as 6m Ω·cm−2.
Undoped, 4µm thick GaN layers grown by Metal Organic Chemical Vapor Deposition were used for fabrication of high stand off voltage (356 V) Schottky diode rectifiers. The figure of merit VRB2/RON, where VRB is the reverse breakdown voltage and RON is the on-resistance, was ~ 4.53 MW-cm−2 at 25°C. The reverse breakdown voltage displayed a negative temperature coefficient, due to an increase in carrier concentration with increasing temperature. Secondary Ion Mass Spectrometry measurements showed that Si and O were the most predominant electrically active impurities present in the GaN.