Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal ...study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80-93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93-98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89-98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.
Plants benefit from associations with a diverse community of root-colonizing microbes. Deciphering the mechanisms underpinning these beneficial services are of interest for improving plant ...productivity. We report a plant-beneficial interaction between Arabidopsis thaliana and the root microbiota under iron deprivation that is dependent on the secretion of plant-derived coumarins. Disrupting this pathway alters the microbiota and impairs plant growth in iron-limiting soil. Furthermore, the microbiota improves iron-limiting plant performance via a mechanism dependent on plant iron import and secretion of the coumarin fraxetin. This beneficial trait is strain specific yet functionally redundant across phylogenetic lineages of the microbiota. Transcriptomic and elemental analyses revealed that this interaction between commensals and coumarins promotes growth by relieving iron starvation. These results show that coumarins improve plant performance by eliciting microbe-assisted iron nutrition. We propose that the bacterial root microbiota, stimulated by secreted coumarins, is an integral mediator of plant adaptation to iron-limiting soils.
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•Coumarins alter the root microbiota and improve plant growth in iron-limiting soil•The microbiota improves plant iron nutrition via a coumarin-dependent mechanism•The iron-beneficial commensal trait is taxonomically widespread but strain specific•Coumarin-microbiota interaction resolves iron starvation and regulates immune response
Iron-limiting soils are widespread, causing significant losses in plant growth and productivity. Harbort et al. show that under iron limitation, plant-secreted coumarin compounds are mediators of a beneficial plant-microbiota interaction. These specialized metabolites alter root microbiota composition and are required for microbiota-mediated plant iron uptake and immune regulation.
Satellite gravity measurements from the Gravity Recovery and Climate Experiment (GRACE) provide new quantitative measures of the 2005 extreme drought event in the Amazon river basin, regarded as the ...worst in over a century. GRACE measures a significant decrease in terrestrial water storage (TWS) in the central Amazon basin in the summer of 2005, relative to the average of the 5 other summer periods in the GRACE era. In contrast, data‐assimilating climate and land surface models significantly underestimate the drought intensity. GRACE measurements are consistent with accumulated precipitation data from satellite remote sensing and are also supported by in situ water‐level data from river gauge stations. This study demonstrates the unique potential of satellite gravity measurements in monitoring large‐scale severe drought and flooding events and in evaluating advanced climate and land surface models.
The recently discovered superconductorUTe2, with a superconducting transition temperatureTcbetween 1.5 and 2 K, is attracting much attention due to strong suspicion of spin-triplet and topological ...superconductivity. Its properties under magnetic field are also remarkable, with field-reinforced (H∥b) and field-induced Hin the(b,c)plane superconducting phases. Here, we report the first complete thermodynamic determination of the phase diagram for fields applied along the three crystallographic directions. For field along the easyaaxis, we uncover a strong negative curvature of the upper critical field very close toTc, revealing a strong suppression of the pairing strength at low magnetic fields. By contrast, measurements performed up to 36 T along the hard magnetizationbaxis confirm a bulk field-reinforced superconducting phase. Most of all, they also reveal the existence of a phase transition line within the superconducting phase. Drastic differences occur between the low-field and high-field phases pointing to different pairing mechanisms. Detailed analysis suggests a possible transition between a low-field spin-triplet to high-field spin-singlet state, a unique case among superconductors.
Key points
The in vivo fetal cardiovascular defence to chronic hypoxia has remained by and large an enigma because no technology has been available to induce significant and prolonged fetal hypoxia ...whilst recording longitudinal changes in fetal regional blood flow as the hypoxic pregnancy is developing.
We introduce a new technique able to maintain chronically instrumented maternal and fetal sheep preparations under isobaric chronic hypoxia for most of gestation, beyond levels that can be achieved by high altitude and of relevance in magnitude to the human intrauterine growth‐restricted fetus.
This technology permits wireless recording in free‐moving animals of longitudinal maternal and fetal cardiovascular function, including beat‐to‐beat alterations in pressure and blood flow signals in regional circulations.
The relevance and utility of the technique is presented by testing the hypotheses that the fetal circulatory brain sparing response persists during chronic fetal hypoxia and that an increase in reactive oxygen species in the fetal circulation is an involved mechanism.
Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean PaO2 levels (11.5 ± 0.6 mmHg) similar to those measured in human fetuses of hypoxic pregnancy. We also created a wireless data acquisition system able to record fetal blood flow signals in addition to fetal blood pressure and heart rate from free moving ewes as the hypoxic pregnancy is developing. We determined in vivo longitudinal changes in fetal cardiovascular function including parallel measurement of fetal carotid and femoral blood flow and oxygen and glucose delivery during the last third of gestation. The ratio of oxygen (from 2.7 ± 0.2 to 3.8 ± 0.8; P < 0.05) and of glucose (from 2.3 ± 0.1 to 3.3 ± 0.6; P < 0.05) delivery to the fetal carotid, relative to the fetal femoral circulation, increased during and shortly after the period of chronic hypoxia. In contrast, oxygen and glucose delivery remained unchanged from baseline in normoxic fetuses. Fetal plasma urate concentration increased significantly during chronic hypoxia but not during normoxia (Δ: 4.8 ± 1.6 vs. 0.5 ± 1.4 μmol l−1, P<0.05). The data support the hypotheses tested and show persisting redistribution of substrate delivery away from peripheral and towards essential circulations in the chronically hypoxic fetus, associated with increases in xanthine oxidase‐derived reactive oxygen species.
Key points
The in vivo fetal cardiovascular defence to chronic hypoxia has remained by and large an enigma because no technology has been available to induce significant and prolonged fetal hypoxia whilst recording longitudinal changes in fetal regional blood flow as the hypoxic pregnancy is developing.
We introduce a new technique able to maintain chronically instrumented maternal and fetal sheep preparations under isobaric chronic hypoxia for most of gestation, beyond levels that can be achieved by high altitude and of relevance in magnitude to the human intrauterine growth‐restricted fetus.
This technology permits wireless recording in free‐moving animals of longitudinal maternal and fetal cardiovascular function, including beat‐to‐beat alterations in pressure and blood flow signals in regional circulations.
The relevance and utility of the technique is presented by testing the hypotheses that the fetal circulatory brain sparing response persists during chronic fetal hypoxia and that an increase in reactive oxygen species in the fetal circulation is an involved mechanism.
To introduce a comprehensive and reliable scoring system for the assessment of whole-knee joint synovitis based on contrast-enhanced (CE) MRI.
Multicenter Osteoarthritis Study (MOST) is a cohort ...study of people with, or at high risk of, knee osteoarthritis (OA). Subjects are an unselected subset of MOST who volunteered for CE-MRI. Synovitis was assessed at 11 sites of the joint. Synovial thickness was scored semiquantitatively: grade 0 (<2 mm), grade 1 (2-4 mm) and grade 2 (>4 mm) at each site. Two musculoskeletal radiologists performed the readings and inter- and intrareader reliability was evaluated. Whole-knee synovitis was assessed by summing the scores from all sites. The association of Western Ontario and McMaster Osteoarthritis Index pain score with this summed score and with the maximum synovitis grade for each site was assessed.
400 subjects were included (mean age 58.8±7.0 years, body mass index 29.5±4.9 kg/m(2), 46% women). For individual sites, intrareader reliability (weighted κ) was 0.67-1.00 for reader 1 and 0.60-1.00 for reader 2. Inter-reader agreement (κ) was 0.67-0.92. For the summed synovitis scores, intrareader reliability (intraclass correlation coefficient ( ICC)) was 0.98 and 0.96 for each reader and inter-reader agreement (ICC) was 0.94. Moderate to severe synovitis in the parapatellar subregion was associated with the higher maximum pain score (adjusted OR (95% CI), 2.8 (1.4 to 5.4) and 3.1 (1.2 to 7.9), respectively).
A comprehensive semiquantitative scoring system for the assessment of whole-knee synovitis is proposed. It is reliable and identifies knees with pain, and thus is a potentially powerful tool for synovitis assessment in epidemiological OA studies.
ABSTRACT
The follow-up timing observations were carried out for 24 pulsars discovered with the Five-hundred-meter Aperture Spherical radio Telescope (FAST) in Commensal Radio Astronomy FAST Survey. ...We report their phase-connected timing ephemeris, polarization pulse profiles, and Faraday rotation measurements. With their spin periods spanning from 2.995 ms to 4.34 s, their period derivatives were determined to spread between 7.996(8) × 10−21 and 9.83(3) × 10−15 s s−1, which imply that they have characteristic ages from 1.97 × 106 to 5.93 × 109 yr. It is inferred that PSRs J0211+4235 and J0518+2431 are beyond the ‘traditional death line’. PSR J0211+4235 is beyond the ‘death valley’. The death line model of Zhang et al. also cannot explain the radio presence of PSR J0211+4235. This suggests that radiation theory needs to be improved. Besides, ten of the 22 canonical pulsars show nulling phenomena. Moreover, PSR J1617+1123 exhibits variation of emission and J0540+4542 shows subpulse drifting. The DM of five pulsars is larger than the estimated by the YMW16 electron density model, which could suggest that electron density models need updates for higher Galactic latitude regions. PSRs J0447+2447 and J1928−0548 are isolated millisecond pulsars. With their flux densities spanning from 5(1)–553(106) μJy, some of these new pulsars found by FAST are distant, dim, and low-$\dot{E}$ ones and are suitable for testing pulsar emission theories.
Switching power semiconductor online junction temperature T j sensing is essential for device switching performance evaluation, device switching control, and device lifetime optimization. The ...contribution of this paper is a detailed evaluation of the implementation issues (including circuit invasiveness, hardware integration, signal processing, and so forth) of different online Ti sensing methods. This paper includes T j sensing methods based on device power dissipation, T j sensing methods based on the "sensoron-die technology," T j sensing methods based on device on-state analysis, and T j sensing methods based on device switching transients. Advantages and limits of these methods are also provided.
Summary Objective To identify the independent relation of synovitis with incident radiographic knee osteoarthritis (OA) after adjusting for other structural factors known to cause synovitis. Design ...We examined MRIs from knees that developed incident radiographic OA from the Multicenter Osteoarthritis Study (MOST) and compared these case knees with controls that did not develop OA. We examined baseline MRIs for knees developing OA at any time up to 84 months follow-up. We scored lesions in cartilage, meniscus, bone marrow and synovitis. Synovitis scores were summed (0–9) across three regions, suprapatellar, infrapatellar and intercondylar region, each of which was scored 0–3. After bivariate analyses examining each factor's association with incidence, we carried out multivariable regression analyses adjusting for age, sex, BMI, alignment and cartilage and meniscal damage. Results We studied 239 case and 731 control knees. In bivariate analyses, cartilage lesions, meniscal damage, synovitis and bone marrow lesions were all risk factors for OA. After multivariable analyses, synovitis was associated with incident OA. A higher synovitis score increased the risk of incident OA (adjusted OR per unit increase 1.1; (95% CI 1.0, 1.2, P = .02)), but increased risk was associated only with synovitis scores of ≥3 (adjusted OR 1.6; 95% CI 1.2, 2.1, P = .003). Conclusions Synovitis, especially when there is a substantial volume within the knee, is an independent cause of OA.
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