Context. Type Ia supernovae (SNe Ia) are widely used to measure the expansion of the Universe. Improving distance measurements of SNe Ia is one technique to better constrain the acceleration of ...expansion and determine its physical nature. Aims. This document develops a new SNe Ia spectral energy distribution (SED) model, called the SUpernova Generator And Reconstructor (SUGAR), which improves the spectral description of SNe Ia, and consequently could improve the distance measurements. Methods. This model was constructed from SNe Ia spectral properties and spectrophotometric data from the Nearby Supernova Factory collaboration. In a first step, a principal component analysis-like method was used on spectral features measured at maximum light, which allowed us to extract the intrinsic properties of SNe Ia. Next, the intrinsic properties were used to extract the average extinction curve. Third, an interpolation using Gaussian processes facilitated using data taken at different epochs during the lifetime of an SN Ia and then projecting the data on a fixed time grid. Finally, the three steps were combined to build the SED model as a function of time and wavelength. This is the SUGAR model. Results. The main advancement in SUGAR is the addition of two additional parameters to characterize SNe Ia variability. The first is tied to the properties of SNe Ia ejecta velocity and the second correlates with their calcium lines. The addition of these parameters, as well as the high quality of the Nearby Supernova Factory data, makes SUGAR an accurate and efficient model for describing the spectra of normal SNe Ia as they brighten and fade. Conclusions. The performance of this model makes it an excellent SED model for experiments like the Zwicky Transient Facility, the Large Synoptic Survey Telescope, or the Wide Field Infrared Survey Telescope.
We discuss the various performance aspects of parallelizing our transient global-scale groundwater model at 30.sup.'' resolution (30 arcsec; â¼ 1 km at the Equator) on large distributed memory ...parallel clusters. This model, referred to as GLOBGM, is the successor of our 5.sup.' (5 arcmin; â¼ 10 km at the Equator) PCR-GLOBWB 2 (PCRaster Global Water Balance model) groundwater model, based on MODFLOW having two model layers. The current version of GLOBGM (v1.0) used in this study also has two model layers, is uncalibrated, and uses available 30.sup.'' PCR-GLOBWB data. Increasing the model resolution from 5.sup.' to 30.sup.'' creates challenges, including increased runtime, memory usage, and data storage that exceed the capacity of a single computer. We show that our parallelization tackles these problems with relatively low parallel hardware requirements to meet the needs of users or modelers who do not have exclusive access to hundreds or thousands of nodes within a supercomputer.
The validity and clinical utility of the concept of “clinical high risk” (CHR) for psychosis have so far been investigated only in risk‐enriched samples in clinical settings. In this population‐based ...prospective study, we aimed – for the first time – to assess the incidence rate of clinical psychosis and estimate the population attributable fraction (PAF) of that incidence for preceding psychosis risk states and DSM‐IV diagnoses of non‐psychotic mental disorders (mood disorders, anxiety disorders, alcohol use disorders, and drug use disorders). All analyses were adjusted for age, gender and education. The incidence rate of clinical psychosis was 63.0 per 100,000 person‐years. The mutually‐adjusted Cox proportional hazards model indicated that preceding diagnoses of mood disorders (hazard ratio, HR=10.67, 95% CI: 3.12‐36.49), psychosis high‐risk state (HR=7.86, 95% CI: 2.76‐22.42) and drug use disorders (HR=5.33, 95% CI: 1.61‐17.64) were associated with an increased risk for clinical psychosis incidence. Of the clinical psychosis incidence in the population, 85.5% (95% CI: 64.6‐94.1) was attributable to prior psychopathology, with mood disorders (PAF=66.2, 95% CI: 33.4‐82.9), psychosis high‐risk state (PAF=36.9, 95% CI: 11.3‐55.1), and drug use disorders (PAF=18.7, 95% CI: –0.9 to 34.6) as the most important factors. Although the psychosis high‐risk state displayed a high relative risk for clinical psychosis outcome even after adjusting for other psychopathology, the PAF was comparatively low, given the low prevalence of psychosis high‐risk states in the population. These findings provide empirical evidence for the “prevention paradox” of targeted CHR early intervention. A comprehensive prevention strategy with a focus on broader psychopathology may be more effective than the current psychosis‐focused approach for achieving population‐based improvements in prevention of psychotic disorders.
Proteins and peptides are increasingly recognized as potential leads for the development of new therapeutics for a variety of human ailments. Due to their relatively specific mode of action, proteins ...and peptides can be administered at relatively low doses for therapeutic effects. As natural biological products, these low doses reduce the risk otherwise caused by other small molecular drugs or larger charged molecules. Unfortunately, their therapeutic potential and clinical application is frequently hampered by various obstacles to their successful delivery. This review discusses the recent developments in the fields of liposome, microparticle and nanoparticle pertinent to protein and peptide delivery covering those systems tested and/or validated in vivo.
Due to the paucity of longitudinal molecular studies of COVID-19, particularly those covering the early stages of infection (Days 1-8 symptom onset), our understanding of host response over the ...disease course is limited. We perform longitudinal single cell RNA-seq on 286 blood samples from 108 age- and sex-matched COVID-19 patients, including 73 with early samples. We examine discrete cell subtypes and continuous cell states longitudinally, and we identify upregulation of type I IFN-stimulated genes (ISGs) as the predominant early signature of subsequent worsening of symptoms, which we validate in an independent cohort and corroborate by plasma markers. However, ISG expression is dynamic in progressors, spiking early and then rapidly receding to the level of severity-matched non-progressors. In contrast, cross-sectional analysis shows that ISG expression is deficient and IFN suppressors such as SOCS3 are upregulated in severe and critical COVID-19. We validate the latter in four independent cohorts, and SOCS3 inhibition reduces SARS-CoV-2 replication in vitro. In summary, we identify complexity in type I IFN response to COVID-19, as well as a potential avenue for host-directed therapy.
Both adulthood stressful life events (SLEs) and liability for schizophrenia have been associated with poor mental and physical health in the general population, but their interaction remains to be ...elucidated to improve population-based health outcomes.
To test whether recent SLEs interact with genetic and environmental liability for schizophrenia in models of mental and physical health.
The Netherlands Mental Health Survey and Incidence Study-2 is a population-based prospective cohort study designed to investigate the prevalence, incidence, course, and consequences of mental disorders in the Dutch general population. Participants were enrolled from November 5, 2007, to July 31, 2009, and followed up with 3 assessments during 9 years. Follow-up was completed on June 19, 2018, and data were analyzed from September 1 to November 1, 2019.
Recent SLEs assessed at each wave and aggregate scores of genetic and environmental liability for schizophrenia: polygenic risk score for schizophrenia (PRS-SCZ) trained using the Psychiatric Genomics Consortium analysis results and exposome score for schizophrenia (ES-SCZ) trained using an independent data set.
Independent and interacting associations of SLEs with ES-SCZ and PRS-SCZ on mental and physical health assessed at each wave using regression coefficients.
Of the 6646 participants included at baseline, the mean (SD) age was 44.26 (12.54) years, and 3672 (55.25%) were female. The SLEs were associated with poorer physical health (B = -3.22 95% CI, -3.66 to -2.79) and mental health (B = -3.68 95% CI, -4.05 to -3.32). Genetic and environmental liability for schizophrenia was associated with poorer mental health (ES-SCZ: B = -3.07 95% CI, -3.35 to -2.79; PRS-SCZ: B = -0.93 95% CI, -1.31 to -0.54). Environmental liability was also associated with poorer physical health (B = -3.19 95% CI, -3.56 to -2.82). The interaction model showed that ES-SCZ moderated the association of SLEs with mental (B = -1.08 95% CI, -1.47 to -0.69) and physical health (B = -0.64 95% CI, -1.11 to -0.17), whereas PRS-SCZ did not. Several sensitivity analyses confirmed these results.
In this study, schizophrenia liability was associated with broad mental health outcomes at the population level. Consistent with the diathesis-stress model, exposure to SLEs, particularly in individuals with high environmental liability for schizophrenia, was associated with poorer health. These findings underline the importance of modifiable environmental factors during the life span for population-based mental health outcomes.
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