A barrier to preventative treatments for psychosis is the absence of accurate identification of persons at highest risk. A blood test that could substantially increase diagnostic accuracy would ...enhance development of psychosis prevention interventions.
The North American Prodrome Longitudinal Study project is a multisite endeavor that aims to better understand predictors and mechanisms for the development of psychosis. In this study, we measured expression of plasma analytes reflecting inflammation, oxidative stress, hormones, and metabolism. A "greedy algorithm" selected analytes that best distinguished persons with clinical high-risk symptoms who developed psychosis (CHR-P; n = 32) from unaffected comparison (UC) subjects (n = 35) and from those who did not develop psychosis during a 2-year follow-up (CHR-NP; n = 40).
The classifier included 15 analytes (selected from 117), with an area under the receiver operating curve for CHR-P vs UC of 0.91 and CHR-P vs CHR-NP of 0.88. Randomly scrambled group membership followed by reconstructions of the entire classifier method yielded consistently weak classifiers, indicating that the true classifier is highly unlikely to be a chance occurrence. Such randomization methods robustly imply the assays contain consistent information distinguishing the groups which was not obscured by the data normalization method and was revealed by classifier construction. These results support the hypothesis that inflammation, oxidative stress, and dysregulation of hypothalamic-pituitary axes may be prominent in the earliest stages of psychosis.
If confirmed in other groups of persons at elevated risk of psychosis, a multiplex blood assay has the potential for high clinical utility.
The very first stars to form in the universe heralded an end to the cosmic dark ages and introduced new physical processes that shaped early cosmic evolution. Until now, it was thought that these ...stars lived short, solitary lives, with only one extremely massive star, or possibly a very wide binary system, forming in each dark-matter minihalo. Here we describe numerical simulations that show that these stars were, to the contrary, often members of tight multiple systems. Our results show that the disks that formed around the first young stars were unstable to gravitational fragmentation, possibly producing small binary and higher-order systems that had separations as small as the distance between Earth and the Sun.
The Earliest Stage of Galactic Star Formation Steinhardt, Charles L.; Rusakov, Vadim; Clark, Thomas H. ...
Astrophysical journal. Letters,
06/2023, Letnik:
949, Številka:
2
Journal Article
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Odprti dostop
Abstract
Using a recently developed technique to estimate gas temperatures (
T
SF
) in star-forming regions from large photometric surveys, we propose a diagram, analogous to the Hertzsprung–Russell ...diagram for individual stars, to probe the evolution of individual galaxies. On this
T
SF
-sSFR (specific star formation rate) diagram, a small fraction of star-forming galaxies appear to be dominated by different feedback mechanisms than typical star-forming galaxies. These galaxies generically have younger stellar populations and lower stellar masses and increase in relative abundance toward higher redshifts, so we argue that these objects are in an earlier stage of galactic star formation. Further, Hubble observations find that these “core-forming” galaxies also exhibit distinct morphology and that tracks on the
T
SF
-sSFR diagram are also a morphological sequence. Thus, unlike starburst phases which can be triggered environmentally, these earliest core-forming galaxies appear to be a stage that typical galaxies go through early in their star formation history. We therefore argue that most galaxies first go through a core formation stage, then subsequently disk formation, and finally become quiescent.
The 2-year risk of psychosis in persons who meet research criteria for a high-risk syndrome is about 15%-25%; improvements in risk prediction accuracy would benefit the development and implementation ...of preventive interventions. The authors sought to assess polygenic risk score (PRS) prediction of subsequent psychosis in persons at high risk and to determine the impact of adding the PRS to a previously validated psychosis risk calculator.
Persons meeting research criteria for psychosis high risk (N=764) and unaffected individuals (N=279) were followed for up to 2 years. The PRS was based on the latest schizophrenia and bipolar genome-wide association studies. Variables in the psychosis risk calculator included stressful life events, trauma, disordered thought content, verbal learning, information processing speed, and family history of psychosis.
For Europeans, the PRS varied significantly by group and was higher in the psychosis converter group compared with both the nonconverter and unaffected groups, but was similar for the nonconverter group compared with the unaffected group. For non-Europeans, the PRS varied significantly by group; the difference between the converters and nonconverters was not significant, but the PRS was significantly higher in converters than in unaffected individuals, and it did not differ between nonconverters and unaffected individuals. The R
(R
adjusted for the rate of disease risk in the population being studied, here assuming a 2-year psychosis risk between 10% and 30%) for Europeans varied between 9.2% and 12.3% and for non-Europeans between 3.5% and 4.8%. The amount of risk prediction information contributed by the addition of the PRS to the risk calculator was less than severity of disordered thoughts and similar to or greater than for other variables. For Europeans, the PRS was correlated with risk calculator variables of information processing speed and verbal memory.
The PRS discriminates psychosis converters from nonconverters and modestly improves individualized psychosis risk prediction when added to a psychosis risk calculator. The schizophrenia PRS shows promise in enhancing risk prediction in persons at high risk for psychosis, although its potential utility is limited by poor performance in persons of non-European ancestry.
The citrus industry is facing an unprecedented challenge from Huanglongbing (HLB). All cultivars can be affected by the HLB-associated bacterium 'Candidatus Liberibacter asiaticus' (CLas) and there ...is no known resistance. Insight into HLB pathogenesis is urgently needed in order to develop effective management strategies. Here, we use Sec-delivered effector 1 (SDE1), which is conserved in all CLas isolates, as a molecular probe to understand CLas virulence. We show that SDE1 directly interacts with citrus papain-like cysteine proteases (PLCPs) and inhibits protease activity. PLCPs are defense-inducible and exhibit increased protein accumulation in CLas-infected trees, suggesting a role in citrus defense responses. We analyzed PLCP activity in field samples, revealing specific members that increase in abundance but remain unchanged in activity during infection. SDE1-expressing transgenic citrus also exhibit reduced PLCP activity. These data demonstrate that SDE1 inhibits citrus PLCPs, which are immune-related proteases that enhance defense responses in plants.
Hemangiomas of infancy can give rise to alarm because of their rapid growth and occasional dramatic appearance. The objective of this study was to investigate the growth pattern of hemangiomas and ...risk factors for residual lesions.
A follow-up study was performed of patients with hemangiomas that were clinically monitored between 1985 and 2000 and who did not receive any treatment. The data were retrieved from medical files. Patients (parents) were asked to complete a questionnaire and invited to our outpatient clinic where the questionnaire was discussed and physical examination was performed. The growth phases of the hemangioma were documented, the timeline of these phases was constructed, and an assessment was made of the residual lesion if present.
In 97 patients, 137 hemangiomas were evaluated. A precursor lesion was present in 48 percent of children. Maximum size was reached in 8 months. Involution started at a median age of 2 years and was completed at a median age of 4 years. Residual lesions were present in 69 percent of cases. Superficial nodular hemangiomas showed significantly more residual lesions (74 percent) than the deep hemangiomas (25 percent) (p < 0.001; odds ratio, 8.4; 95 percent confidence interval, 2.4 to 29.1). Untreated infection, ulceration, or bleeding produced a scar in 97 percent of the cases.
Epidermal invasion of the hemangioma is of predictive value for residual lesions. There is no correlation between the growth pattern of a hemangioma and the risk for a residual lesion. This may add to a more detailed prediction of outcome and may help to decide which patient should be treated or not.
Approximately 20%-35% of individuals 12-35 years old who meet criteria for a prodromal risk syndrome convert to psychosis within 2 years. However, this estimate ignores the fact that clinical ...high-risk cases vary considerably in risk. The authors sought to create a risk calculator, based on profiles of risk indicators, that can ascertain the probability of conversion to psychosis in individual patients.
The study subjects were 596 clinical high-risk participants from the second phase of the North American Prodrome Longitudinal Study who were followed up to the time of conversion to psychosis or last contact (up to 2 years). The predictors examined were limited to those that are supported by previous studies and are readily obtainable in general clinical settings. Time-to-event regression was used to build a multivariate model predicting conversion, with internal validation using 1,000 bootstrap resamples.
The 2-year probability of conversion to psychosis was 16%. Higher levels of unusual thought content and suspiciousness, greater decline in social functioning, lower verbal learning and memory performance, slower speed of processing, and younger age at baseline each contributed to individual risk for psychosis. Stressful life events, trauma, and family history of schizophrenia were not significant predictors. The multivariate model achieved a concordance index of 0.71 and, as reported in an article by Carrión et al., published concurrently with this one, was validated in an independent external data set. The results are instantiated in a web-based risk prediction tool envisioned to be most useful in research protocols involving the psychosis prodrome.
A risk calculator comparable in accuracy to those for cardiovascular disease and cancer is available to predict individualized conversion risks in newly ascertained clinical high-risk cases. Given that the risk calculator can be validly applied only for patients who screen positive on the Structured Clinical Interview for Psychosis Risk Syndromes, which requires training to administer, its most immediate uses will be in research on psychosis risk factors and in research-driven clinical (prevention) trials.
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