Psychosis commonly develops in adolescence or early adulthood. Youths at clinical high risk (CHR) for psychosis exhibit similar, subtle symptoms to those with schizophrenia (SZ). Malfunctioning ...neurotransmitter systems, such as glutamate, are implicated in the disease progression of psychosis. Yet, in vivo imaging techniques for measuring glutamate across the cortex are limited. Here, we use a novel 7 Tesla MRI glutamate imaging technique (GluCEST) to estimate changes in glutamate levels across cortical and subcortical regions in young healthy individuals and ones on the psychosis spectrum. Individuals on the psychosis spectrum (PS; n=19) and healthy young individuals (HC; n=17) underwent MRI imaging at 3 and 7 T. At 7 T, a single slice GluCEST technique was used to estimate in vivo glutamate. GluCEST contrast was compared within and across the subcortex, frontal, parietal and occipital lobes. Subcortical (χ
(1)=4.65, P=0.031) and lobular (χ
(1)=5.17, P=0.023) GluCEST contrast levels were lower in PS compared with HC. Abnormal GluCEST contrast levels were evident in both CHR (n=14) and SZ (n=5) subjects, and correlated differentially, across regions, with clinical symptoms. Our findings describe a pattern of abnormal brain neurochemistry early in the course of psychosis. Specifically, CHR and young SZ exhibit diffuse abnormalities in GluCEST contrast attributable to a major contribution from glutamate. We suggest that neurochemical profiles of GluCEST contrast across cortex and subcortex may be considered markers of early psychosis. GluCEST methodology thus shows promise to further elucidate the progression of the psychosis disease state.
Summary
Background
Crohn's disease recurs in the majority of patients after intestinal resection.
Aim
To compare the relative efficacy of thiopurines and anti‐TNF therapy in patients at high risk of ...disease recurrence.
Methods
As part of a larger study comparing post‐operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine‐intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment.
Results
A total of 101 patients 50% male; median (IQR) age 36 (25–46) years were included. There were no differences in disease history between thiopurine‐ and adalimumab‐treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2–i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab‐treated patients intention‐to‐treat (ITT); P = 0.028 or 24 of 62 (39%) vs. 3 of 24 (13%) respectively per‐protocol analysis (PPA); P = 0.020. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab).
Conclusions
In Crohn's disease patients at high risk of post‐operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.
Truncation mutations of the receptor cytoplasmic domain for colony-stimulating factor 3 (CSF3R) are frequently seen in severe congenital neutropenia, whereas activating missense mutations affecting ...the extracellular domain (exon 14) have been described in hereditary neutrophilia and chronic neutrophilic leukemia (CNL). In order to clarify mutational frequency, specificity and phenotypic associations, we sequenced CSF3R exons 14-17 in 54 clinically suspected cases of CNL (n=35) or atypical chronic myeloid leukemia (aCML; n=19). Central review of these cases confirmed WHO-defined CNL in 12 patients, monoclonal gammopathy (MG)-associated CNL in 5 and WHO-defined aCML in 9. A total of 14 CSF3R mutations were detected in 13 patients, including 10 with CSF3RT618I (exon 14 mutation, sometimes annotated as CSF3R T595I). CSF3RT618I occurred exclusively in WHO-defined CNL with a mutational frequency of 83% (10 of 12 cases). CSF3R mutations were not seen in aCML or MG-associated CNL. CSF3RT618I was also absent among 170 patients with primary myelofibrosis (PMF; n=76) or chronic myelomonocytic leukemia (CMML; n=94). SETBP1 mutational frequencies in WHO-defined CNL, aCML, CMML and PMF were 33, 0, 7 and 3%, respectively. Four CSF3RT618I-mutated cases co-expressed SETBP1 mutations. We conclude that CSF3RT618I is a highly sensitive and specific molecular marker for CNL and should be incorporated into current diagnostic criteria.
Background
The impact of cardiorespiratory comorbidity on operative outcomes after esophagectomy remains controversial. This study investigated the effect of cardiorespiratory comorbidity on ...postoperative complications for patients treated for esophageal or gastroesophageal junction cancer.
Patients and Methods
A European multicenter cohort study from five high-volume esophageal cancer centers including patients treated between 2010 and 2017 was conducted. The effect of cardiorespiratory comorbidity and respiratory function upon postoperative outcomes was assessed.
Results
In total 1590 patients from five centers were included; 274 (17.2%) had respiratory comorbidity, and 468 (29.4%) had cardiac comorbidity. Respiratory comorbidity was associated with increased risk of overall postoperative complications, anastomotic leak, pulmonary complications, pneumonia, increased Clavien–Dindo score, and critical care and hospital length of stay. After neoadjuvant chemoradiotherapy, respiratory comorbidity was associated with increased risk of anastomotic leak odds ratio (OR) 1.83, 95% confidence interval (CI) 1.11–3.04, pneumonia (OR 1.65, 95% CI 1.10–2.47), and any pulmonary complication (OR 1.52, 95% CI 1.04–2.22), an effect which was not observed following neoadjuvant chemotherapy or surgery alone. Cardiac comorbidity was associated with increased risk of cardiovascular and pulmonary complications, respiratory failure, and Clavien–Dindo score ≥ IIIa. Among all patients, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio > 70% was associated with reduced risk of overall postoperative complications, cardiovascular complications, atrial fibrillation, pulmonary complications, and pneumonia.
Conclusions
The results of this study suggest that cardiorespiratory comorbidity and impaired pulmonary function are associated with increased risk of postoperative complications after esophagectomy performed in high-volume European centers. Given the observed interaction with neoadjuvant approach, these data indicate a potentially modifiable index of perioperative risk.
The awareness of the increase in greenhouse gas emissions has resulted in the development of new technologies with lower emissions and technologies that can accommodate capture and sequestration of ...carbon dioxide. For existing coal-fired combustion plants there are two main options for CO
2 capture: removal of nitrogen from flue gases or removal of nitrogen from air before combustion to obtain a gas stream ready for geo-sequestration. In oxy-fuel combustion, fuel is combusted in pure oxygen rather than air. This technology recycles flue gas back into the furnace to control temperature and makeup the volume of the missing N
2 to ensure there is sufficient gas to maintain the temperature and heat flux profiles in the boiler. A further advantage of the technology revealed in pilot-scale tests is substantially reduced NO
x
emissions. For coal-fired combustion, the technology was suggested in the eighties, however, recent developments have led to a renewed interest in the technology. This paper provides a comprehensive review of research that has been undertaken, gives the status of the technology development and assessments providing comparisons with other power generation options, and suggests research needs.
The New Horizons spacecraft flew past the Kuiper Belt object (486958) Arrokoth (also known as 2014 MU69) in January 2019. Because of the great distance to the outer Solar System and limited ...bandwidth, it will take until late 2020 to downlink all the spacecraft's observations back to Earth. Three papers in this issue analyze recently downlinked data, including the highest-resolution images taken during the encounter (see the Perspective by Jewitt). Spencer et al. examined Arrokoth's geology and geophysics using stereo imaging, dated the surface using impact craters, and produced a geomorphological map. Grundy et al. investigated the composition of the surface using color imaging and spectroscopic data and assessed Arrokoth's thermal emission using microwave radiometry. McKinnon et al. used simulations to determine how Arrokoth formed: Two gravitationally bound objects gently spiraled together during the formation of the Solar System. Together, these papers determine the age, composition, and formation process of the most pristine object yet visited by a spacecraft.
Context:
The mechanism by which PTH is controlled during and after exercise is poorly understood due to insufficient temporal frequency of measurements.
Objective:
The objective of the study was to ...examine the temporal pattern of PTH, PO4, albumin-adjusted calcium, and Ca2+ during and after exercise.
Design and Setting:
This was a laboratory-based study with a crossover design, comparing 30 minutes of running at 55%, 65%, and 75% maximal oxygen consumption, followed by 2.5 hours of recovery. Blood was obtained at baseline, after 2.5, 5, 7.5, 10, 15, 20, 25, and 30 minutes of exercise, and after 2.5, 5, 7.5, 10, 15, 20, 25, 30, 60, 90, and 150 minutes of recovery.
Participants:
Ten men (aged 23 ± 1 y, height 1.82 ± 0.07 m, body mass 77.0 ± 7.5 kg) participated.
Main Outcome Measures:
PTH, PO4, albumin-adjusted calcium, and Ca2+ were measured.
Results:
Independent of intensity, PTH concentrations decreased with the onset of exercise (−21% to −33%; P ≤ .001), increased thereafter, and were higher than baseline by the end of exercise at 75% maximal oxygen consumption (+52%; P ≤ .001). PTH peaked transiently after 5–7.5 minutes of recovery (+73% to +110%; P ≤ .001). PO4 followed a similar temporal pattern to PTH, and Ca2+ followed a similar but inverse pattern to PTH. PTH was negatively correlated with Ca2+ across all intensities (r = −0.739 to −0.790; P ≤ .001). When PTH was increasing, the strongest cross-correlation was with Ca2+ at 0 lags (3.5 min) (r = −0.902 to −0.950); during recovery, the strongest cross-correlation was with PO4 at 0 lags (8 min) (r = 0.987–0.995).
Conclusions:
PTH secretion during exercise and recovery is controlled by a combination of changes in Ca2+ and PO4 in men.
PTH rapidly decreased and then increased during exercise, it peaked in the first minutes of recovery before decreasing below baseline. Changes in Ca2+ and PO4 were related to the changes in PTH.
The Pluto system was recently explored by NASA's New Horizons spacecraft, making closest approach on 14 July 2015. Pluto's surface displays diverse landforms, terrain ages, albedos, colors, and ...composition gradients. Evidence is found for a water-ice crust, geologically young surface units, surface ice convection, wind streaks, volatile transport, and glacial flow. Pluto's atmosphere is highly extended, with trace hydrocarbons, a global haze layer, and a surface pressure near 10 microbars. Pluto's diverse surface geology and long-term activity raise fundamental questions about how small planets remain active many billions of years after formation. Pluto's large moon Charon displays tectonics and evidence for a heterogeneous crustal composition; its north pole displays puzzling dark terrain. Small satellites Hydra and Nix have higher albedos than expected.
Observed electron distribution functions of the solar wind permanently exhibit three different components: a thermal core and a suprathermal halo, which are always present at all pitch angles, and a ...sharply magnetic field aligned “strahl” which is usually anti‐sunward moving. Whereas Coulomb collisions can explain the relative isotropy of the core population, the origin of the halo population, and more specifically the origin of its sunward directed part, remains unknown. In this study we present the radial evolution of the electron velocity distribution functions in the fast solar wind between 0.3 and 1.5 AU. For this purpose we combine data measured separately by the Helios, Wind, and Ulysses spacecraft. We compute average distributions over distance and normalize them to 1 AU to remove the effects of the solar wind expansion. Then we model separately the core, halo, and strahl components to compute their relative number density or fraction of the total electron density. We observe that, while the core fractional density remains roughly constant with radial distance, the halo and strahl fractional densities vary in an opposite way. The relative number of halo electrons is increasing, while the relative number of strahl electrons is decreasing with distance. Therefore we provide, for the first time, strong evidences for a scenario that is commonly assumed: the heliospheric electron halo population consists partly of electrons that have been scattered out of the strahl.
The atmosphere of Pluto as observed by New Horizons Gladstone, G. Randall; Stern, S. Alan; Ennico, Kimberly ...
Science (American Association for the Advancement of Science),
03/2016, Letnik:
351, Številka:
6279
Journal Article
Recenzirano
Odprti dostop
Observations made during the New Horizons flyby provide a detailed snapshot of the current state of Pluto's atmosphere. Whereas the lower atmosphere (at altitudes of less than 200 kilometers) is ...consistent with ground-based stellar occultations, the upper atmosphere is much colder and more compact than indicated by pre-encounter models. Molecular nitrogen (N2) dominates the atmosphere (at altitudes of less than 1800 kilometers or so), whereas methane (CH4), acetylene (C2H2), ethylene (C2H4), and ethane (C2H6) are abundant minor species and likely feed the production of an extensive haze that encompasses Pluto. The cold upper atmosphere shuts off the anticipated enhanced-Jeans, hydrodynamic-like escape of Pluto's atmosphere to space. It is unclear whether the current state of Pluto's atmosphere is representative of its average state--over seasonal or geologic time scales.
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