Adult symptoms of ASD and ADHD in relation to alcohol use: Potential roles of transdiagnostic features

Attention Deficit Hyperactivity Disorder (ADHD) is the most common comorbidity in Autism Spectrum Disorder (ASD). ADHD is a risk factor for alcohol misuse whereas ASD is often regarded as protective; however, research on ASD and alcohol use has yielded conflicting findings, sometimes implicating the role of comorbid ADHD. The possibility that certain transdiagnostic features (i.e., characteristics associated with multiple disorders) may underlie relationships of both disorders to alcohol use in adults was examined in the present study. A nonclinical young adult sample of 248 alcohol users (117 men, 131 women) completed validated self-report measures of ASD and ADHD symptoms as well as the transdiagnostic features alexithymia, impulsivity, and negative moods. ASD and ADHD symptoms were normally distributed, suggesting that the respective disorders represent extreme, dysfunctional ends of population distributions of symptoms. Path analysis indicated that the significant positive association between ASD and ADHD symptom measures was fully mediated by alexithymia, impulsivity, and negative moods. Hierarchical regression and path analysis indicated that the positive relationship between ADHD symptoms and alcohol use severity was fully mediated by transdiagnostic features, particularly alexithymia and impulsivity, whereas the relationship between ASD and alcohol use severity was positively mediated by these features (especially alexithymia), with a highly significant and negative direct effect. Present findings may help reconcile previous conflicting evidence on the relationship of ASD to alcohol use, and the role of comorbid ADHD, by emphasizing the roles of alexithymia and impulsivity in both ASD and ADHD as transdiagnostic traits promoting excessive drinking.</p

Comparison of histomorphology and DNA preservation produced by fixatives in the veterinary diagnostic laboratory setting

Histopathology is the most useful tool for diagnosis of a number of diseases, especially cancer. To be effective, histopathology requires that tissues be fixed prior to processing. Formalin is currently the most common histologic fixative, offering many advantages: it is cheap, readily available, and pathologists are routinely trained to examine tissues fixed in formalin. However, formalin fixation substantially degrades tissue DNA, hindering subsequent use in diagnostics and research. We therefore evaluated three alternative fixatives, TissueTek® Xpress® Molecular Fixative, modified methacarn, and PAXgene®, all of which have been proposed as formalin alternatives, to determine their suitability for routine use in a veterinary diagnostic laboratory. This was accomplished by examining the histomorphology of sections produced from fixed tissues as well as the ability to amplify fragments from extracted DNA. Tissues were sampled from two dogs and four cats, fixed for 24–48 h, and processed routinely. While all fixatives produced acceptable histomorphology, formalin had significantly better morphologic characteristics than the other three fixatives. Alternative fixatives generally had better DNA amplification than formalin, although results varied somewhat depending on the tissue examined. While no fixative is yet ready to replace formalin, the alternative fixatives examined may be useful as adjuncts to formalin in diagnostic practices

PSFs of coadded images

We provide a detailed exploration of the connection between choice of coaddition schemes and the point-spread function (PSF) of the resulting coadded images. In particular, we investigate what properties of the coaddition algorithm lead to the final coadded image having a well-defined PSF. The key elements of this discussion are as follows: 1. We provide an illustration of how linear coaddition schemes can produce a coadd that lacks a well-defined PSF even for relatively simple scenarios and choices of weight functions. 2. We provide a more formal demonstration of the fact that a linear coadd only has a well-defined PSF in the case that either (a) each input image has the same PSF or (b) the coadd is produced with weights that are independent of the signal. 3. We discuss some reasons that two plausible nonlinear coaddition algorithms (median and clipped-mean) fail to produce a consistent PSF profile for stars. 4. We demonstrate that all nonlinear coaddition procedures fail to produce a well-defined PSF for extended objects. In the end, we conclude that, for any purpose where a well-defined PSF is desired, one should use a linear coaddition scheme with weights that do not correlate with the signal and are approximately uniform across typical objects of interest.Comment: 13 pages, 4 figures; pedagogical article for submission to the Open Journal of Astrophysic

Deep learning for necrosis detection using canine perivascular wall tumour whole slide images

Necrosis seen in histopathology Whole Slide Images is a major criterion that contributes towards scoring tumour grade which then determines treatment options. However conventional manual assessment suffers from inter-operator reproducibility impacting grading precision. To address this, automatic necrosis detection using AI may be used to assess necrosis for final scoring that contributes towards the final clinical grade. Using deep learning AI, we describe a novel approach for automating necrosis detection in Whole Slide Images, tested on a canine Soft Tissue Sarcoma (cSTS) data set consisting of canine Perivascular Wall Tumours (cPWTs). A patch-based deep learning approach was developed where different variations of training a DenseNet-161 Convolutional Neural Network architecture were investigated as well as a stacking ensemble. An optimised DenseNet-161 with post-processing produced a hold-out test F1-score of 0.708 demonstrating state-of-the-art performance. This represents a novel first-time automated necrosis detection method in the cSTS domain as well specifically in detecting necrosis in cPWTs demonstrating a significant step forward in reproducible and reliable necrosis assessment for improving the precision of tumour grading

Determining the Repertoire of Immunodominant Proteins via Whole-Genome Amplification of Intracellular Pathogens

Culturing many obligate intracellular bacteria is difficult or impossible. However, these organisms have numerous adaptations allowing for infection persistence and immune system evasion, making them some of the most interesting to study. Recent advancements in genome sequencing, pyrosequencing and Phi29 amplification, have allowed for examination of whole-genome sequences of intracellular bacteria without culture. We have applied both techniques to the model obligate intracellular pathogen Anaplasma marginale and the human pathogen Anaplasma phagocytophilum, in order to examine the ability of phi29 amplification to determine the sequence of genes allowing for immune system evasion and long-term persistence in the host. When compared to traditional pyrosequencing, phi29-mediated genome amplification had similar genome coverage, with no additional gaps in coverage. Additionally, all msp2 functional pseudogenes from two strains of A. marginale were detected and extracted from the phi29-amplified genomes, highlighting its utility in determining the full complement of genes involved in immune evasion

Measurement of telescope transmission using a Collimated Beam Projector

With the increasingly large number of type Ia supernova being detected by current-generation survey telescopes, and even more expected with the upcoming Rubin Observatory Legacy Survey of Space and Time, the precision of cosmological measurements will become limited by systematic uncertainties in flux calibration rather than statistical noise. One major source of systematic error in determining SNe Ia color evolution (needed for distance estimation) is uncertainty in telescope transmission, both within and between surveys. We introduce here the Collimated Beam Projector (CBP), which is meant to measure a telescope transmission with collimated light. The collimated beam more closely mimics a stellar wavefront as compared to flat-field based instruments, allowing for more precise handling of systematic errors such as those from ghosting and filter angle-of-incidence dependence. As a proof of concept, we present CBP measurements of the StarDICE prototype telescope, achieving a standard (1 sigma) uncertainty of 3 % on average over the full wavelength range measured with a single beam illumination

Flavin Mononucleotide as a Biomarker of Organ Quality-A Pilot Study.

BACKGROUND: Flavin mononucleotide (FMN), released from damaged mitochondrial complex I during hypothermic liver perfusion, has been shown to be predictive of 90-day graft loss. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) are used for organ reconditioning and quality assessment before transplantation. This pilot study aimed to investigate the changes of FMN levels during normothermic reperfusion of kidneys, livers, and lungs and examine whether FMN could serve as a biomarker to predict posttransplant allograft quality. METHODS: FMN concentrations, in perfusates collected during NMP of kidneys, abdominal NRP, and ex vivo lung perfusion, were measured using fluorescence spectrometry and correlated to the available perfusion parameters and clinical outcomes. RESULTS: Among 7 transplanted kidneys out of the 11 kidneys that underwent NMP, FMN levels at 60 minutes of NMP were significantly higher in the allografts that developed delayed graft function and primary nonfunction (P = 0.02). Fifteen livers from 23 circulatory death donors that underwent NRP were deemed suitable for transplantation. Their FMN levels at 30 minutes of NRP were significantly lower than those not procured for transplantation (P = 0.004). In contrast, little FMN was released during the 8 lung perfusions. CONCLUSIONS: This proof of concept study suggested that FMN in the perfusates of kidney NMP has the potential to predict posttransplant renal function, whereas FMN at 30 minutes of NRP predicts whether a liver would be accepted for transplantation. More work is required to validate the role of FMN as a putative biomarker to facilitate safe and reliable decision-making before embarking on transplantation.NIHR BTR

Towards a systems-level view of cerebellar function::the interplay between cerebellum, basal ganglia and cortex

Contains fulltext : 170319.pdf (Publisher’s version ) (Open Access)Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field

A GMBCG Galaxy Cluster Catalog of 55,424 Rich Clusters from SDSS DR7

We present a large catalog of optically selected galaxy clusters from the application of a new Gaussian Mixture Brightest Cluster Galaxy (GMBCG) algorithm to SDSS Data Release 7 data. The algorithm detects clusters by identifying the red sequence plus Brightest Cluster Galaxy (BCG) feature, which is unique for galaxy clusters and does not exist among field galaxies. Red sequence clustering in color space is detected using an Error Corrected Gaussian Mixture Model. We run GMBCG on 8240 square degrees of photometric data from SDSS DR7 to assemble the largest ever optical galaxy cluster catalog, consisting of over 55,000 rich clusters across the redshift range from 0.1 < z < 0.55. We present Monte Carlo tests of completeness and purity and perform cross-matching with X-ray clusters and with the maxBCG sample at low redshift. These tests indicate high completeness and purity across the full redshift range for clusters with 15 or more members.Comment: Updated to match the published version. The catalog can be accessed from: http://home.fnal.gov/~jghao/gmbcg_sdss_catalog.htm

Nuclear Morphometry using a Deep Learning-based Algorithm has Prognostic Relevance for Canine Cutaneous Mast Cell Tumors

Variation in nuclear size and shape is an important criterion of malignancy for many tumor types; however, categorical estimates by pathologists have poor reproducibility. Measurements of nuclear characteristics (morphometry) can improve reproducibility, but manual methods are time consuming. In this study, we evaluated fully automated morphometry using a deep learning-based algorithm in 96 canine cutaneous mast cell tumors with information on patient survival. Algorithmic morphometry was compared with karyomegaly estimates by 11 pathologists, manual nuclear morphometry of 12 cells by 9 pathologists, and the mitotic count as a benchmark. The prognostic value of automated morphometry was high with an area under the ROC curve regarding the tumor-specific survival of 0.943 (95% CI: 0.889 - 0.996) for the standard deviation (SD) of nuclear area, which was higher than manual morphometry of all pathologists combined (0.868, 95% CI: 0.737 - 0.991) and the mitotic count (0.885, 95% CI: 0.765 - 1.00). At the proposed thresholds, the hazard ratio for algorithmic morphometry (SD of nuclear area $\geq 9.0 \mu m^2$) was 18.3 (95% CI: 5.0 - 67.1), for manual morphometry (SD of nuclear area $\geq 10.9 \mu m^2$) 9.0 (95% CI: 6.0 - 13.4), for karyomegaly estimates 7.6 (95% CI: 5.7 - 10.1), and for the mitotic count 30.5 (95% CI: 7.8 - 118.0). Inter-rater reproducibility for karyomegaly estimates was fair ($\kappa$ = 0.226) with highly variable sensitivity/specificity values for the individual pathologists. Reproducibility for manual morphometry (SD of nuclear area) was good (ICC = 0.654). This study supports the use of algorithmic morphometry as a prognostic test to overcome the limitations of estimates and manual measurements