At-risk mental state for psychosis : identification and current treatment approaches

© The Royal College of Psychiatrists 2016. The concept of an ‘at-risk mental state’ for psychosis arose from previous work attempting to identify a putative psychosis prodrome. In this article we summarise the current criteria used to identify ‘at-risk’ individuals, such as the ultra-highrisk (UHR) criteria, and the further identification of important clinical risk factors or biomarkers to improve prediction of who might develop a psychotic disorder. We also discuss important ethical issues in classifying and treating at-risk individuals, current treatment trials in this area and what treatment current services can offer

Illumina mate-paired DNA sequencing-library preparation using Cre-Lox recombination

Standard Illumina mate-paired libraries are constructed from 3- to 5-kb DNA fragments by a blunt-end circularization. Sequencing reads that pass through the junction of the two joined ends of a 3-5-kb DNA fragment are not easy to identify and pose problems during mapping and de novo assembly. Longer read lengths increase the possibility that a read will cross the junction. To solve this problem, we developed a mate-paired protocol for use with Illumina sequencing technology that uses Cre-Lox recombination instead of blunt end circularization. In this method, a LoxP sequence is incorporated at the junction site. This sequence allows screening reads for junctions without using a reference genome. Junction reads can be trimmed or split at the junction. Moreover, the location of the LoxP sequence in the reads distinguishes mate-paired reads from spurious paired-end reads. We tested this new method by preparing and sequencing a mate-paired library with an insert size of 3 kb from Saccharomyces cerevisiae. We present an analysis of the library quality statistics and a new bio-informatics tool called DeLoxer that can be used to analyze an IlluminaCre-Lox mate-paired data set. We also demonstrate how the resulting data significantly improves a de novo assembly of the S. cerevisiae genome

Organ preservation and survival by clinical response grade in patients with rectal cancer treated with total neoadjuvant therapy: A secondary analysis of the OPRA randomized clinical trial

IMPORTANCE: Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment. OBJECTIVE: To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade. DESIGN, SETTING, AND PARTICIPANTS: This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023. INTERVENTION: Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP. MAIN OUTCOMES AND MEASURES: OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test. RESULTS: There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P \u3c .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival. CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02008656

Representations of Time Coordinates in FITS

In a series of three previous papers, formulation and specifics of the representation of World Coordinate Transformations in FITS data have been presented. This fourth paper deals with encoding time. Time on all scales and precisions known in astronomical datasets is to be described in an unambiguous, complete, and self-consistent manner. Employing the well--established World Coordinate System (WCS) framework, and maintaining compatibility with the FITS conventions that are currently in use to specify time, the standard is extended to describe rigorously the time coordinate. World coordinate functions are defined for temporal axes sampled linearly and as specified by a lookup table. The resulting standard is consistent with the existing FITS WCS standards and specifies a metadata set that achieves the aims enunciated above.Comment: FITS WCS Paper IV: Time. 27 pages, 11 table

Intense Electromagnetic Outbursts from Collapsing Hypermassive Neutron Stars

We study the gravitational collapse of a magnetized neutron star using a novel numerical approach able to capture both the dynamics of the star and the behavior of the surrounding plasma. In this approach, a fully general relativistic magnetohydrodynamics implementation models the collapse of the star and provides appropriate boundary conditions to a force-free model which describes the stellar exterior. We validate this strategy by comparing with known results for the rotating monopole and aligned rotator solutions and then apply it to study both rotating and non-rotating stellar collapse scenarios, and contrast the behavior with what is obtained when employing the electrovacuum approximation outside the star. The non-rotating electrovacuum collapse is shown to agree qualitatively with a Newtonian model of the electromagnetic field outside a collapsing star. We illustrate and discuss a fundamental difference between the force-free and electrovacuum solutions, involving the appearance of large zones of electric-dominated field in the vacuum case. This provides a clear demonstration of how dissipative singularities appear generically in the non-linear time-evolution of force-free fluids. In both the rotating and non-rotating cases, our simulations indicate that the collapse induces a strong electromagnetic transient. In the case of sub-millisecond rotation, the magnetic field experiences strong winding and the transient carries much more energy. This result has important implications for models of gamma-ray bursts.Comment: 28 pages, 20 figures (quality lowered to reduce sizes). Improved initial data and matching condition results in a lower, but still important, energy emission. Added appendix with a discussion on effects of transition laye

Quantum Monte Carlo calculations of spectroscopic overlaps in A≤7A \leq 7 nuclei

We present Green's function Monte Carlo calculations of spectroscopic overlaps for $A \leq 7$ nuclei. The realistic Argonne v18 two-nucleon and Illinois-7 three-nucleon interactions are used to generate the nuclear states. The overlap matrix elements are extrapolated from mixed estimates between variational Monte Carlo and Green's function Monte Carlo wave functions. The overlap functions are used to obtain spectroscopic factors and asymptotic normalization coefficients, and they can serve as an input for low-energy reaction calculations

Wavelets and their application to digital signal processing in ultrsaonic NDE

As the use of digital based ultrasonic testing systems becomes more prevalent, there will be an increased emphasis on the development of digital signal processing techniques. In the past, various Fourier based digital signal processing approaches have been formulated and applied in the ultrasonic nondestructive evaluation (NDE) research community. In many cases, the inherent inability of Fourier methods to handle non-stationary signals has been exposed as the Fourier methods are applied to non-stationary ultrasonic signals. Our intent is to investigate the application of wavelet based signals processing techniques to a variety of problems in ultrasonic NDE. Wavelet methods have a number of potential advantage over Fourier methods including the inherent ability of wavelets to deal with non-stationary signals

The Carnegie Astrometric Planet Search Program

We are undertaking an astrometric search for gas giant planets and brown dwarfs orbiting nearby low mass dwarf stars with the 2.5-m du Pont telescope at the Las Campanas Observatory in Chile. We have built two specialized astrometric cameras, the Carnegie Astrometric Planet Search Cameras (CAPSCam-S and CAPSCam-N), using two Teledyne Hawaii-2RG HyViSI arrays, with the cameras' design having been optimized for high accuracy astrometry of M dwarf stars. We describe two independent CAPSCam data reduction approaches and present a detailed analysis of the observations to date of one of our target stars, NLTT 48256. Observations of NLTT 48256 taken since July 2007 with CAPSCam-S imply that astrometric accuracies of around 0.3 milliarcsec per hour are achievable, sufficient to detect a Jupiter-mass companion orbiting 1 AU from a late M dwarf 10 pc away with a signal-to-noise ratio of about 4. We plan to follow about 100 nearby (primarily within about 10 pc) low mass stars, principally late M, L, and T dwarfs, for 10 years or more, in order to detect very low mass companions with orbital periods long enough to permit the existence of habitable, Earth-like planets on shorter-period orbits. These stars are generally too faint and red to be included in ground-based Doppler planet surveys, which are often optimized for FGK dwarfs. The smaller masses of late M dwarfs also yield correspondingly larger astrometric signals for a given mass planet. Our search will help to determine whether gas giant planets form primarily by core accretion or by disk instability around late M dwarf stars.Comment: 48 pages, 9 figures. in press, Publ. Astron. Soc. Pacifi

The Giant Flare of December 27, 2004 from SGR 1806-20

The giant flare of December 27, 2004 from SGR 1806-20 represents one of the most extraordinary events captured in over three decades of monitoring the gamma-ray sky. One measure of the intensity of the main peak is its effect on X- and gamma-ray instruments. RHESSI, an instrument designed to study the brightest solar flares, was completely saturated for ~0.5 s following the start of the main peak. A fortuitous alignment of SGR 1806-20 near the Sun at the time of the giant flare, however, allowed RHESSI a unique view of the giant flare event, including the precursor, the main peak decay, and the pulsed tail. Since RHESSI was saturated during the main peak, we augment these observations with Wind and RHESSI particle detector data in order to reconstruct the main peak as well. Here we present detailed spectral analysis and evolution of the giant flare. We report the novel detection of a relatively soft fast peak just milliseconds before the main peak, whose timescale and sizescale indicate a magnetospheric origin. We present the novel detection of emission extending up to 17 MeV immediately following the main peak, perhaps revealing a highly-extended corona driven by the hyper-Eddington luminosities. The spectral evolution and pulse evolution during the tail are presented, demonstrating significant magnetospheric twist and evolution during this phase. Blackbody radii are derived for every stage of the flare, which show remarkable agreement despite the range of luminosities and temperatures covered. Finally, we place significant upper limits on afterglow emission in the hundreds of seconds following the giant flare.Comment: 32 pages, 14 figures, submitted to Ap

TruncTrimmer: A First Step Towards Automating Standard Bioinformatic Analysis

Bioinformatic analysis is a time-consuming process for labs performing research on various microbiomes. Researchers use tools like Qiime2 to help standardize the bioinformatic analysis methods, but even large, extensible platforms like Qiime2 have drawbacks due to the attention required by researchers. In this project, we propose to automate additional standard lab bioinformatic procedures by eliminating the existing manual process of determining the trim and truncate locations for paired end 2 sequences. We introduce a new Qiime2 plugin called TruncTrimmer to automate the process that usually requires the researcher to make a decision on where to trim and truncate manually after importing and demultiplexing sequences in the Qiime2 pipeline. By automating this process and removing the need for manual interaction by the researcher, this plugin provides another opportunity to automate another standard bioinformatic analysis procedure