Enhancing Early Detection: Improving Autism Spectrum Disorder Diagnostic Processes

Early identification and intervention of Autism Spectrum Disorder (ASD) has been well-established as extremely important for developmental outcomes, as the most efficacious treatments for the disorder occur prior to five years of age (McCarty & Frye, 2020). In this paper, divided into two chapters, I examine potential changes to the ASD diagnostic process to aid the goal of early intervention. In Chapter 1, I discuss how modifications to current gold-standard diagnostic tools could help with this goal. Efforts to improve early detection and intervention for Autism Spectrum Disorder (ASD) have led to the development of screening and diagnostic tools such as M-CHAT-R, ADOS, and ADEC. However, despite the progress in this field, the average diagnostic age remains significantly older than optimal (McCarty & Frye, 2020). This literature review delves into the limitations of existing tools and proposes modifications aimed at enhancing early detection, such as revising scoring systems, incorporating assessments for motor issues, and improving cohesion between screening and diagnosis. In Chapter 2, I expand upon how utilizing the motor domain in the ASD diagnostic process could aid early detection. While research has consistently demonstrated a link between ASD and delays in the motor domain, the mainstream screening practices often neglect motor considerations. Specific trends in infant motor development, such as balance (Odeh et al., 2020), gait, and postural control (Fulceri et al., 2019), have been identified as predictive of ASD diagnosis. Moreover, motor difficulties have been found to impact outcomes in domains core to ASD itself (Libertus & Violi, 2016; Iverson et al., 2018). Yet, less than 1% of individuals with ASD receive clinical recognition for motor impairments, and even fewer receive targeted therapeutic interventions (Bhat, 2020; Licari et al., 2019). Incorporating motor assessment into current screening practices and modifying diagnostic labeling to include motor concerns could improve early recognition of ASD

Solar variability and climate

Recent precise observations of solar global parameters are used to calibrate an upgraded solar model which takes into account magnetic fields in the solar interior. Historical data about sunspot numbers (from 1500 to the present) and solar radius changes (between 1715 and 1979) are used to compute solar variability on years to centuries timescales. The results show that although the 11 year variability of the total irradiance is of the order of 0.1%, additional, longer lived changes of the order of 0.1% may have occurred in the past centuries. These could, for example, account for the occurrence of climate excursions such as little ice ages.Comment: LaTeX, JGR preprint with AGU++ v16.b and AGUTeX 5.0, use packages graphicx; 6 pages, 4 figures, submitted to JGR-Space physic

An integrated approach to infer the mechanisms of mate choice for size

Size-assortative mating and sexual selection on size are common across species. Since both may be a result of mate choice, mate choice based on size should also be a widespread process. This behaviour is, however, rarely studied directly and thus the biological causes that determine size-based mate choice are poorly understood. To address this, we studied the size-based mate choice in an intertidal snail, Echinolittorina malaccana, that has been used as a model to understand this process. Previous studies, assuming a quantitative Gaussian mating preference function, have inferred that mate choice in this snail is caused by a size similarity mechanism (males prefer to mate with females slightly larger than themselves). To further test and quantify this proposed mechanism, we conducted mate choice experiments with alternative designs (single, male and multiple choice) in the laboratory and compared the results to mate choice data observed in natural populations. This integrated approach allowed us to elucidate the mechanism of mate choice by evaluating alternative mating models that best fitted the observed data of various designs. Results confirmed the similarity-based mechanism but showed deviations at extreme size classes. The single choice design indicated that mate choice was exercised during one-on-one maleefemale interactions, but the strength of mate choice increased with the presence of additional individuals (males in the male choice design, and both males and females in the multiplechoice design). Multiple-choice experiments are, therefore, the most valuable and useful design to infer how males choose mates in the wild, as they best mimic the natural scenario and the results are the most similar to those observed in natural populations. To elucidate the mechanisms causing this male choice for particular female sizes, the next steps are to identify the genetic basis as well as potential physiological benefits associated with choosing slightly larger females.Xunta de Galicia | Ref. ED431C 2020-05Ministerio de Economía, Industria y Competitividad | Ref. CGL2016-75482-

New compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites:an open resource

Using whole-cell phenotypic assays, the GlaxoSmithKline high-throughput screening (HTS) diversity set of 1.8 million compounds was screened against the three kinetoplastids most relevant to human disease, i.e. Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. Secondary confirmatory and orthogonal intracellular anti-parasiticidal assays were conducted, and the potential for non-specific cytotoxicity determined. Hit compounds were chemically clustered and triaged for desirable physicochemical properties. The hypothetical biological target space covered by these diversity sets was investigated through bioinformatics methodologies. Consequently, three anti-kinetoplastid chemical boxes of ~200 compounds each were assembled. Functional analyses of these compounds suggest a wide array of potential modes of action against kinetoplastid kinases, proteases and cytochromes as well as potential host–pathogen targets. This is the first published parallel high throughput screening of a pharma compound collection against kinetoplastids. The compound sets are provided as an open resource for future lead discovery programs, and to address important research questions.The support and funding of Tres Cantos Open Lab Foundation is gratefully acknowledgedPeer reviewe

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual\u27s risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig\u27s potential to enhance clinical therapeutic innovation to improve human health. (Figure presented.)

Improving pregnancy outcomes in humans through studies in sheep

Experimental studies that are relevant to human pregnancy rely on the selection of appropriate animal models as an important element in experimental design. Consideration of the strengths and weaknesses of any animal model of human disease is fundamental to effective and meaningful translation of preclinical research. Studies in sheep have made significant contributions to our understanding of the normal and abnormal development of the fetus. As a model of human pregnancy, studies in sheep have enabled scientists and clinicians to answer questions about the etiology and treatment of poor maternal, placental, and fetal health and to provide an evidence base for translation of interventions to the clinic. The aim of this review is to highlight the advances in perinatal human medicine that have been achieved following translation of research using the pregnant sheep and fetus

Implementation and testing of the first prompt search for gravitational wave transients with electromagnetic counterparts

Aims. A transient astrophysical event observed in both gravitational wave (GW) and electromagnetic (EM) channels would yield rich scientific rewards. A first program initiating EM follow-ups to possible transient GW events has been developed and exercised by the LIGO and Virgo community in association with several partners. In this paper, we describe and evaluate the methods used to promptly identify and localize GW event candidates and to request images of targeted sky locations. Methods. During two observing periods (Dec 17 2009 to Jan 8 2010 and Sep 2 to Oct 20 2010), a low-latency analysis pipeline was used to identify GW event candidates and to reconstruct maps of possible sky locations. A catalog of nearby galaxies and Milky Way globular clusters was used to select the most promising sky positions to be imaged, and this directional information was delivered to EM observatories with time lags of about thirty minutes. A Monte Carlo simulation has been used to evaluate the low-latency GW pipeline's ability to reconstruct source positions correctly. Results. For signals near the detection threshold, our low-latency algorithms often localized simulated GW burst signals to tens of square degrees, while neutron star/neutron star inspirals and neutron star/black hole inspirals were localized to a few hundred square degrees. Localization precision improves for moderately stronger signals. The correct sky location of signals well above threshold and originating from nearby galaxies may be observed with ~50% or better probability with a few pointings of wide-field telescopes.Comment: 17 pages. This version (v2) includes two tables and 1 section not included in v1. Accepted for publication in Astronomy & Astrophysic

Search for Gravitational Waves from Low Mass Compact Binary Coalescence in LIGO's Sixth Science Run and Virgo's Science Runs 2 and 3

We report on a search for gravitational waves from coalescing compact binaries using LIGO and Virgo observations between July 7, 2009 and October 20, 2010. We searched for signals from binaries with total mass between 2 and 25 solar masses; this includes binary neutron stars, binary black holes, and binaries consisting of a black hole and neutron star. The detectors were sensitive to systems up to 40 Mpc distant for binary neutron stars, and further for higher mass systems. No gravitational-wave signals were detected. We report upper limits on the rate of compact binary coalescence as a function of total mass, including the results from previous LIGO and Virgo observations. The cumulative 90%-confidence rate upper limits of the binary coalescence of binary neutron star, neutron star- black hole and binary black hole systems are 1.3 x 10^{-4}, 3.1 x 10^{-5} and 6.4 x 10^{-6} Mpc^{-3}yr^{-1}, respectively. These upper limits are up to a factor 1.4 lower than previously derived limits. We also report on results from a blind injection challenge.Comment: 11 pages, 5 figures. For a repository of data used in the publication, go to: . Also see the announcement for this paper on ligo.org at: <http://www.ligo.org/science/Publication-S6CBCLowMass/index.php

Sensitivity to Gravitational Waves from Compact Binary Coalescences Achieved during LIGO's Fifth and Virgo's First Science Run

We summarize the sensitivity achieved by the LIGO and Virgo gravitational wave detectors for compact binary coalescence (CBC) searches during LIGO's fifth science run and Virgo's first science run. We present noise spectral density curves for each of the four detectors that operated during these science runs which are representative of the typical performance achieved by the detectors for CBC searches. These spectra are intended for release to the public as a summary of detector performance for CBC searches during these science runs.Comment: 12 pages, 5 figure

Search for gravitational waves associated with the InterPlanetary Network short gamma ray bursts

We outline the scientific motivation behind a search for gravitational waves associated with short gamma ray bursts detected by the InterPlanetary Network (IPN) during LIGO's fifth science run and Virgo's first science run. The IPN localisation of short gamma ray bursts is limited to extended error boxes of different shapes and sizes and a search on these error boxes poses a series of challenges for data analysis. We will discuss these challenges and outline the methods to optimise the search over these error boxes.Comment: Methods paper; Proceedings for Eduardo Amaldi 9 Conference on Gravitational Waves, July 2011, Cardiff, U