Publications by authors named "Margaret King"

Background: Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival.

Methods: The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK.

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Article Synopsis
  • Formal thought disorder (FTD) is a key symptom of schizophrenia, but its exact neurobiological causes and correlation with brain volume loss are still unclear, which this study seeks to address using a large cohort of patients and controls.
  • The research focuses on differentiating between positive, negative, and total formal thought disorder while investigating brain structural changes and their cellular bases using virtual histology tools.
  • Findings reveal distinct neural networks for positive and negative FTD, with negative FTD showing preserved orbitofrontal thickness and both FTD types linked to unique cellular fingerprint patterns, advancing our understanding of the disorder.
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Article Synopsis
  • A study investigates the connection between formal thought disorder (FTD) symptoms in schizophrenia and brain volume deficiencies, using data from 752 individuals with schizophrenia and 1256 controls.
  • The research identifies separate neural networks associated with positive and negative FTD, revealing differences in brain structures affected by each type of symptom.
  • Findings show that negative FTD is linked to specific neuronal and astrocyte cell types, while positive FTD is associated with microglial cells, enhancing understanding of the biological mechanisms behind these symptoms.
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Article Synopsis
  • Formal thought disorder (FTD) significantly impacts schizophrenia, yet its neurobiological causes, particularly the connection between FTD symptoms and brain volume changes, are largely unexplored.
  • This study, involving a large cohort of 752 individuals with schizophrenia and 1256 controls, aims to clarify the neuroanatomical aspects of positive and negative FTD and their cellular foundations using advanced virtual histology techniques.
  • Results revealed two distinct neural networks for FTD: one linked to negative symptoms, with preserved orbitofrontal thickness, and another for positive symptoms, affecting lateral temporal areas; each network had unique cellular signatures, highlighting different underlying mechanisms for these psychotic symptoms.
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Objective: To test the association of parents' concerns with early intervention (EI) developmental services outcomes including evaluation, eligibility, and enrollment in services.

Method: We collected survey data on parents' concerns and EI service use data from a sample of 428 children referred to EI from 2016 to 2018 in 6 Oregon primary care clinics serving lower-income families as part of a developmental and autism spectrum disorder screening intervention. We assessed EI service use trajectories and associations of the presence of parent concern, age of child at the time of parents' concerns, number of concerns, and type of provider concern, with EI evaluation, EI eligibility, and enrollment in EI services, using bivariate testing and multivariable logistic regression.

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Latino children experience delays in access to diagnosis and treatment of autism spectrum disorder. Primary care-based screening of all children for autism spectrum disorder and referring them for services may reduce racial/ethnic differences and improve care. REAL-START, a yearlong screening intervention, was effective in increasing screening for autism spectrum disorder and general developmental delays, increasing therapy referrals, and shortening time for developmental assessment in primary care clinics with Latino patients.

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Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group.

Methods: The study included data from 4474 individuals with schizophrenia (mean age, 32.

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Objective: Fragile X syndrome (FXS) has been the neurodevelopmental disorder with the most active translation of preclinical breakthroughs into clinical trials. This process has led to a critical assessment of outcome measures, which resulted in a comprehensive review published in 2013. Nevertheless, the disappointing outcome of several recent phase III drug trials in FXS, and parallel efforts at evaluating behavioral endpoints for trials in autism spectrum disorder (ASD), has emphasized the need for re-assessing outcome measures and revising recommendations for FXS.

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This data descriptor describes a repository of openly shared data from an experiment to assess inter-individual differences in default mode network (DMN) activity. This repository includes cross-sectional functional magnetic resonance imaging (fMRI) data from the Multi Source Interference Task, to assess DMN deactivation, the Moral Dilemma Task, to assess DMN activation, a resting state fMRI scan, and a DMN neurofeedback paradigm, to assess DMN modulation, along with accompanying behavioral and cognitive measures. We report technical validation from n=125 participants of the final targeted sample of 180 participants.

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Purpose: Presence is the essence of professional nursing in the nurse-patient connection. Nursing students have little exposure to strategies fostering presence. This pilot study explored students' perceptions of strategies to encourage presence in the classroom.

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In this paper we propose a web-based approach for quick visualization of big data from brain magnetic resonance imaging (MRI) scans using a combination of an automated image capture and processing system, nonlinear embedding, and interactive data visualization tools. We draw upon thousands of MRI scans captured via the COllaborative Imaging and Neuroinformatics Suite (COINS). We then interface the output of several analysis pipelines based on structural and functional data to a t-distributed stochastic neighbor embedding (t-SNE) algorithm which reduces the number of dimensions for each scan in the input data set to two dimensions while preserving the local structure of data sets.

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Data sharing and mediation across disparate neuroimaging repositories requires extensive effort to ensure that the different domains of data types are referred to by commonly agreed upon terms. Within the SchizConnect project, which enables querying across decentralized databases of neuroimaging, clinical, and cognitive data from various studies of schizophrenia, we developed a model for each data domain, identified common usable terms that could be agreed upon across the repositories, and linked them to standard ontological terms where possible. We had the goal of facilitating both the current user experience in querying and future automated computations and reasoning regarding the data.

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In many scientific domains, including neuroimaging studies, there is a need to obtain increasingly larger cohorts to achieve the desired statistical power for discovery. However, the economics of imaging studies make it unlikely that any single study or consortia can achieve the desired sample sizes. What is needed is an architecture that can easily incorporate additional studies as they become available.

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Aim: We report on outcomes and significant grade 3-4 late toxicities between January 1999 and October 2006 following introduction of multi-phase treatment and effect of shielding in treatment of cervical cancer with concurrent chemoradiation.

Patients And Methods: Radiotherapy dose by phase, recurrence, survival and toxicity data was collated by a retrospective review of clinical notes. Shielding information was retrieved from original planning films.

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SchizConnect (www.schizconnect.org) is built to address the issues of multiple data repositories in schizophrenia neuroimaging studies.

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Neuroimaging data collection is inherently expensive. Maximizing the return on investment in neuroimaging studies requires that neuroimaging data be re-used whenever possible. In an effort to further scientific knowledge, the COINS Data Exchange (DX) (http://coins.

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Brain glycogen synthase kinase-3 (GSK3) is hyperactive in several neurological conditions that involve impairments in both cognition and neurogenesis. This raises the hypotheses that hyperactive GSK3 may directly contribute to impaired cognition, and that this may be related to deficiencies in neural precursor cells (NPC). To study the effects of hyperactive GSK3 in the absence of disease influences, we compared adult hippocampal NPC proliferation and performance in three cognitive tasks in male and female wild-type (WT) mice and GSK3 knockin mice, which express constitutively active GSK3.

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Neuroscientists increasingly need to work with big data in order to derive meaningful results in their field. Collecting, organizing and analyzing this data can be a major hurdle on the road to scientific discovery. This hurdle can be lowered using the same technologies that are currently revolutionizing the way that cultural and social media sites represent and share information with their users.

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Accurate data collection at the ground level is vital to the integrity of neuroimaging research. Similarly important is the ability to connect and curate data in order to make it meaningful and sharable with other investigators. Collecting data, especially with several different modalities, can be time consuming and expensive.

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Recent research has provided evidence of a link between behavioral measures of social cognition (SC) and neural and genetic correlates. Differences in face processing and variations in the oxytocin receptor (OXTR) gene have been associated with SC deficits and autism spectrum disorder (ASD) traits. Much work has examined the qualitative differences between those with ASD and typically developing (TD) individuals, but very little has been done to quantify the natural variation in ASD-like traits in the typical population.

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Efforts to identify meaningful functional imaging-based biomarkers are limited by the ability to reliably characterize inter-individual differences in human brain function. Although a growing number of connectomics-based measures are reported to have moderate to high test-retest reliability, the variability in data acquisition, experimental designs, and analytic methods precludes the ability to generalize results. The Consortium for Reliability and Reproducibility (CoRR) is working to address this challenge and establish test-retest reliability as a minimum standard for methods development in functional connectomics.

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Background: Identifying feasible therapeutic interventions is crucial for ameliorating the intellectual disability and other afflictions of fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism. Hippocampal glycogen synthase kinase-3 (GSK3) is hyperactive in the mouse model of FXS (FX mice), and hyperactive GSK3 promotes locomotor hyperactivity and audiogenic seizure susceptibility in FX mice, raising the possibility that specific GSK3 inhibitors may improve cognitive processes.

Methods: We tested if specific GSK3 inhibitors improve deficits in N-methyl-D-aspartate receptor-dependent long-term potentiation at medial perforant path synapses onto dentate granule cells and dentate gyrus-dependent cognitive behavioral tasks.

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Impairment of cognitive processes is a devastating outcome of many diseases, injuries, and drugs affecting the central nervous system (CNS). Most often, very little can be done by available therapeutic interventions to improve cognitive functions. Here we review evidence that inhibition of glycogen synthase kinase-3 (GSK3) ameliorates cognitive deficits in a wide variety of animal models of CNS diseases, including Alzheimer's disease, Fragile X syndrome, Down syndrome, Parkinson's disease, spinocerebellar ataxia type 1, traumatic brain injury, and others.

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