Publications by authors named "Robert Abbott"

253 Publications

Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients: a case series and review of the literature.

Clin Infect Dis 2021 May 14. Epub 2021 May 14.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego (UCSD), La Jolla, CA 92093, USA.

Background: Increased inflammation has been well defined in COVID-19, while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets.

Methods: Blood was obtained serially from critically ill COVID-19 patients for eleven days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis and cytokine levels were assessed. Lung tissue was obtained immediately post-mortem for immunostaining. Pubmed searches for neutrophils, lung and COVID-19 yielded ten peer-reviewed research articles in English.

Results: Elevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified both at first measurement and across hospitalization (p<0.0001). COVID neutrophils had exaggerated oxidative burst (p<0.0001), NETosis (p<0.0001) and phagocytosis (p<0.0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of SARS-CoV-2 infected lungs available for examination (2 out of 5). While elevations in IL-8 and ANC correlated with disease severity, plasma IL-8 levels alone correlated with death.

Conclusions: Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data shows that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.
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http://dx.doi.org/10.1093/cid/ciab437DOI Listing
May 2021

Sleep Duration, Sleep Apnea, and Gray Matter Volume.

J Geriatr Psychiatry Neurol 2021 Jan 29:891988720988918. Epub 2021 Jan 29.

Institute of Human Genomic Study, Korea University College of Medicine, Ansan City, South Korea.

This study aimed to evaluate the effect of sleep duration on brain structures in the presence versus absence of sleep apnea in middle-aged and older individuals. The study investigated a population-based sample of 2,560 individuals, aged 49-80 years. The presence of sleep apnea and self-reported sleep duration were examined in relation to gray matter volume (GMV) in total and lobar brain regions. We identified ranges of sleep duration associated with maximal GMV using quadratic regression and bootstrap sampling. A significant quadratic association between sleep duration and GMV was observed in total and lobar brain regions of men with sleep apnea. In the fully adjusted model, optimal sleep durations associated with peak GMV between brain regions ranged from 6.7 to 7.0 hours. Shorter and longer sleep durations were associated with lower GMV in total and 4 sub-regions of the brain in men with sleep apnea.
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http://dx.doi.org/10.1177/0891988720988918DOI Listing
January 2021

Association of pericardial adipose tissue with left ventricular structure and function: a region-specific effect?

Cardiovasc Diabetol 2021 01 25;20(1):26. Epub 2021 Jan 25.

Division of Cardiology, Korea University Ansan Hospital, 123, Jeokgeum-ro, Danwon-gu, Gyeonggi-do, 15355, Ansan, South Korea.

Background: The independent role of pericardial adipose tissue (PAT) as an ectopic fat associated with cardiovascular disease (CVD) remains controversial. This study aimed to determine whether PAT is associated with left ventricular (LV) structure and function independent of other markers of general obesity.

Methods: We studied 2471 participants (50.9 % women) without known CVD from the Korean Genome Epidemiology Study, who underwent 2D-echocardiography with tissue Doppler imaging (TDI) and computed tomography measurement for PAT.

Results: Study participants with more PAT were more likely to be men and had higher cardiometabolic indices, including blood pressure, glucose, and cholesterol levels (all P < 0.001). Greater pericardial fat levels across quartiles of PAT were associated with increased LV mass index and left atrial volume index (all P < 0.001) and decreased systolic (P = 0.015) and early diastolic (P < 0.001) TDI velocities, except for LV ejection fraction. These associations remained after a multivariable-adjusted model for traditional CV risk factors and persisted even after additional adjustment for general adiposity measures, such as waist circumference and body mass index. PAT was also the only obesity index independently associated with systolic TDI velocity (P < 0.001).

Conclusions: PAT was associated with subclinical LV structural and functional deterioration, and these associations were independent of and stronger than with general and abdominal obesity measures.
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http://dx.doi.org/10.1186/s12933-021-01219-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836147PMC
January 2021

A longitudinal observational population-based study of brain volume associated with changes in sleep timing from middle to late-life.

Sleep 2021 04;44(4)

College of Medicine, Korea University, Republic of Korea.

Study Objectives: Sleep behaviors are related to brain structure and function, but the impact of long-term changes in sleep timing on brain health has not been clearly addressed. The purpose of this study was to examine the association of longitudinal changes in sleep timing from middle to late-life with gray matter volume (GMV), an important marker of brain aging.

Methods: We enrolled 1798 adults (aged 49-82 years, men 54.6%) who underwent magnetic resonance imaging (MRI) between 2011 and 2014. Midsleep time (MST) on free days corrected for sleep debt on workdays was adopted as a marker of sleep timing. Data on MST were available at the time of MRI assessment and at examinations that were given 9 years earlier (2003-2004). Longitudinal changes in MST over the 9-year period were derived and categorized into quartiles. Subjects in quartile 1 were defined as "advancers" (MST advanced ≥ 1 h) while those in quartile 4 were defined as "delayers" (MST delayed ≥ 0.2 h). Quartiles 2-3 defined a reference group (MST change was considered modest). The relationship of GMV with MST changes over 9 years was investigated.

Results: Nine-year change in MST were significantly associated with GMV. Compared to the reference group, advancers had smaller GMVs in the frontal and temporal regions. A delay in MST was also associated with smaller cerebellar GMV.

Conclusions: In middle-to-late adulthood, the direction of change in MST is associated with GMV. While advancers and delayers in MST tend to present lower GMV, associations appear to differ across brain regions.
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http://dx.doi.org/10.1093/sleep/zsaa233DOI Listing
April 2021

Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity.

Cell 2020 11 16;183(4):996-1012.e19. Epub 2020 Sep 16.

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA. Electronic address:

Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4 and CD8 T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4 and CD8 T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4 and CD8 T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4 T cell, CD8 T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.
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http://dx.doi.org/10.1016/j.cell.2020.09.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494270PMC
November 2020

B cells expressing authentic naive human VRC01-class BCRs can be recruited to germinal centers and affinity mature in multiple independent mouse models.

Proc Natl Acad Sci U S A 2020 09 1;117(37):22920-22931. Epub 2020 Sep 1.

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037;

Animal models of human antigen-specific B cell receptors (BCRs) generally depend on "inferred germline" sequences, and thus their relationship to authentic naive human B cell BCR sequences and affinities is unclear. Here, BCR sequences from authentic naive human VRC01-class B cells from healthy human donors were selected for the generation of three BCR knockin mice. The BCRs span the physiological range of affinities found in humans, and use three different light chains (VK3-20, VK1-5, and VK1-33) found among subclasses of naive human VRC01-class B cells and HIV broadly neutralizing antibodies (bnAbs). The germline-targeting HIV immunogen eOD-GT8 60mer is currently in clinical trial as a candidate bnAb vaccine priming immunogen. To attempt to model human immune responses to the eOD-GT8 60mer, we tested each authentic naive human VRC01-class BCR mouse model under rare human physiological B cell precursor frequency conditions. B cells with high (HuGL18) or medium (HuGL17) affinity BCRs were primed, recruited to germinal centers, and they affinity matured, and formed memory B cells. Precursor frequency and affinity interdependently influenced responses. Taken together, these experiments utilizing authentic naive human VRC01-class BCRs validate a central tenet of germline-targeting vaccine design and extend the overall concept of the reverse vaccinology approach to vaccine development.
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http://dx.doi.org/10.1073/pnas.2004489117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502816PMC
September 2020

Multifaceted Effects of Antigen Valency on B Cell Response Composition and Differentiation In Vivo.

Immunity 2020 09 27;53(3):548-563.e8. Epub 2020 Aug 27.

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA. Electronic address:

How antigen valency affects B cells in vivo during immune responses is not well understood. Here, using HIV immunogens with defined valencies ranging from 1 to 60, we investigated the role of antigen valency during different phases of B cell responses in vivo. Highly multimerized immunogens preferentially rapidly activated cognate B cells, with little affinity discrimination. This led to strong early induction of the transcription factors IRF4 (interferon regulatory factor 4) and Bcl6, driving both early extrafollicular plasma cell and germinal center responses, in a CD4 T-cell-dependent manner, involving B cells with a broad range of affinities. Low-valency antigens induced smaller effector B cell responses, with preferential recruitment of high-affinity B cells. Thus, antigen valency has multifaceted effects on B cell responses and can dictate affinity thresholds and competitive landscapes for B cells in vivo, with implications for vaccine design.
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http://dx.doi.org/10.1016/j.immuni.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451196PMC
September 2020

Efficacy of a Multimodal Online Lifestyle Intervention for Depressive Symptoms and Quality of Life in Individuals With a History of Major Depressive Disorder.

Cureus 2020 Jul 8;12(7):e9061. Epub 2020 Jul 8.

Psychiatry and Behavioral Sciences, Independent Researcher, Miami, USA.

Background Major depressive disorder (MDD) is a complex bio-psycho-social syndrome that affects millions of individuals and is one of the leading causes of impaired quality of life (QOL). In addition to the symptoms of depression and low mood, many individuals with MDD also suffer from isolation without the sense of a supportive, surrounding community. Given the challenges of treating individuals with MDD, social isolation and a lack of communal connection, this randomized controlled trial was designed to determine the efficacy of a multimodal, online and community-based lifestyle intervention for improving depressive symptoms and QOL in individuals with a history of MDD. Materials and methods The study enrolled 71 female or male participants between the ages of 20 and 64 with a self-reported BMI between 18.4 and 34.9 kg/mand a history of MDD. Individuals were randomized to either participate in a 44-day multimodal, online, community-based lifestyle intervention or placed on a wait list where they would complete the intervention at a later date. The multimodal intervention involved a self-directed learning program where individuals were guided to make lifestyle changes including adopting a whole-foods diet, increasing movement, and adopting stress management and mindfulness practices. All participants completed the 36-Item Short Form Health Survey (SF-36), the Cleveland Clinic Center for Functional Medicine's Medical Symptoms Questionnaire (MSQ), and the Patient Health Questionnaire-9 (PHQ-9) before and after the online program to assess health-related QOL, overall symptom burden, and depressive symptom burden, respectively.  Results A total of 37 participants were randomized to participate in the multimodal intervention with 26 completing all three study questionnaires at both study time points; 34 participants were randomized to the wait list control group with 27 completing all three study questionnaires at both study time points. There were no clinically or statistically significant differences between the control group or the intervention group at baseline. The control group showed no clinically nor statistically significant changes in the MSQ, PHQ-9 or any of the eight subdomains of the SF-36 from the beginning to the end of the 10-week study period. When compared to the control group, the intervention group showed statistically and clinically significant improvements in median (M) scores of the SF-36 subdomains of vitality and mental health, and clinically but not statistically significant improvements in the subdomain of emotional role functioning. There were additional statistically and clinically significant improvements in the mean score of the MSQ and M scores of the PHQ-9 (treatment pre-intervention M = 10.5, inter-quartile range [IQR] = 14, to treatment post-intervention M = 5, IQR = 8.25; control pre-intervention M = 15, IQR = 8, to control post-intervention M = 13.5, IQR = 12.5). Conclusions  Our randomized controlled study provides evidence for the role of a multimodal, online and community-based lifestyle intervention to improve depressive symptoms, QOL, and total symptom burden in individuals with a history of MDD. Given the growing challenges of effectively supporting individuals suffering with MDD, it appears critical to further explore the utilization of novel, multimodal and self-directed lifestyle interventions.
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http://dx.doi.org/10.7759/cureus.9061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346300PMC
July 2020

Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model.

Science 2020 08 15;369(6506):956-963. Epub 2020 Jun 15.

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.
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http://dx.doi.org/10.1126/science.abc7520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299280PMC
August 2020

Outcomes of Childhood Preventive Intervention Across 2 Generations: A Nonrandomized Controlled Trial.

JAMA Pediatr 2020 08;174(8):764-771

Social Development Research Group, School of Social Work, University of Washington, Seattle.

Importance: Trials of preventive interventions for children that were implemented in the 1980s have reported sustained positive outcomes on behavioral and health outcomes into adulthood, years after the end of the intervention. This present study examines whether intervention in childhood may show sustained benefits across generations.

Objective: To examine possible intervention outcomes on the offspring of individuals (now parents) who participated in the Raising Healthy Children preventive intervention as children in the elementary grades.

Design, Setting, And Participants: This nonrandomized controlled trial was conducted in public elementary schools serving high-crime areas in Seattle, Washington. The panel originated in Seattle but was followed up locally and in out-of-state locations over time. Data analyzed in this study were collected from September 1980 to June 2011, with follow-up of the firstborn offspring (aged 1 through 22 years) of 182 parents who had been in the full intervention vs control conditions in childhood. Their children were assessed across 7 waves in 2 blocks (2002-2006 and 2009-2011). Data were analyzed for this article from September 2018 through January 2019.

Interventions: In grades 1 through 6, the Raising Healthy Children intervention provided elementary school teachers with methods of classroom management and instruction, first-generation (G1) parents with skills to promote opportunities for children's active involvement in the classroom and family, and second-generation (G2) child with social and emotional skills training.

Main Outcomes And Measures: Outcomes examined in the third-generation (G3) offspring were self-regulation (emotion, attention, and behavioral regulation), cognitive capabilities, and social capabilities. Risk behaviors, including substance use and delinquency, were examined from age 6 years to study completion. Early onset of sexual activity was examined from age 13 years to study completion. Intent-to-treat analyses controlled for potential confounding factors.

Results: A total of 182 G3 children were included in this analysis (72 in the full intervention and 110 in the control condition; mean age at first wave of data collection, 7 [range, 1-13] years). Significant differences in the offspring of intervention parents were observed across 4 domains: improved early child developmental functioning (ages 1-5 years; significant standardized β range, 0.45-0.56), lower teacher-rated behavioral problems (ages 6-18 years; significant standardized β range, -0.39 to -0.46), higher teacher-rated academic skills and performance (ages 6-18 years; significant standardized β range, 0.34-0.49), and lower child-reported risk behavior (ages 6-18 years; odds ratio for any drug use [alcohol, cigarettes, or marijuana], 0.27 [95% CI, 0.10-0.73]).

Conclusions And Relevance: To our knowledge, this is the first study to report significant intervention differences in the offspring of participants in a universal childhood preventive intervention. Cost-benefit analyses have examined the benefits of childhood intervention in the target generation. The present study suggests that additional benefits can be realized in the next generation as well.

Trial Registration: ClinicalTrials.gov Identifier: NCT04075019.
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http://dx.doi.org/10.1001/jamapediatrics.2020.1310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281355PMC
August 2020

Rapid isolation of potent SARS-CoV-2 neutralizing antibodies and protection in a small animal model.

bioRxiv 2020 May 15. Epub 2020 May 15.

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

The development of countermeasures to prevent and treat COVID-19 is a global health priority. In under 7 weeks, we enrolled a cohort of SARS-CoV-2-recovered participants, developed neutralization assays to interrogate serum and monoclonal antibody responses, adapted our high throughput antibody isolation, production and characterization pipeline to rapidly screen over 1000 antigen-specific antibodies, and established an animal model to test protection. We report multiple highly potent neutralizing antibodies (nAbs) and show that passive transfer of a nAb provides protection against high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs define protective epitopes to guide vaccine design.
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http://dx.doi.org/10.1101/2020.05.11.088674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263516PMC
May 2020

Factors in B cell competition and immunodominance.

Immunol Rev 2020 07 1;296(1):120-131. Epub 2020 Jun 1.

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA.

The majority of all vaccines work by inducing protective antibody responses. The mechanisms by which the B cells responsible for producing protective antibodies are elicited to respond are not well understood. Interclonal B cell competition to complex antigens, particularly in germinal centers, has emerged as an important hurdle in designing effective vaccines. This review will focus on recent advances in understanding the roles of B cell precursor frequency, B cell receptor affinity for antigen, antigen avidity, and other factors that can substantially alter the outcomes of B cell responses to complex antigens. Understanding the interdependence of these fundamental factors that affect B cell responses can inform current vaccine design efforts for pathogens with complex proteins as candidate immunogens such as HIV, influenza, and coronaviruses.
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http://dx.doi.org/10.1111/imr.12861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641103PMC
July 2020

Neck Circumference and Cerebral Gray Matter Volume.

Alzheimer Dis Assoc Disord 2020 Oct-Dec;34(4):306-312

Institute of Human Genomic Study, Korea University College of Medicine, Ansan-si.

Background: While obesity is linked with brain atrophy and dementia incidence, associations with regional adiposity are uncertain. Our goal was to determine whether cerebral gray matter volume is related to neck circumference (NC), a measure of regional adiposity having unique relationships with metabolic disorders and cardiovascular disease.

Methods: Magnetic resonance imaging and NC were cross-sectionally assessed from 2011 to 2014 in a population-based sample of 2916 men and women in the Korean Genome and Epidemiology Study.

Results: For men, NC was inversely associated with total and regional gray matter in the frontal, temporal, and occipital lobes after adjusting for age and intracranial brain volume. Associations were especially strong in the presence of diabetes. With further adjustment for indices of body composition and other characteristics, total and frontal gray matter in diabetic men were lowered by 6.1 mL (95% confidence interval: 2.5-9.7, P=0.004) and 2.9 mL (95% confidence interval: 1.0-4.9, P=0.017), respectively, per SD increase in NC (2.3 cm). For men without diabetes, and in all women, associations were less apparent.

Conclusions: In men with diabetes, NC was inversely associated with cerebral gray matter volume. The link between neck anthropometry and brain aging in diabetic men warrants further consideration.
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http://dx.doi.org/10.1097/WAD.0000000000000386DOI Listing
June 2020

Engineered immunogen binding to alum adjuvant enhances humoral immunity.

Nat Med 2020 03 17;26(3):430-440. Epub 2020 Feb 17.

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.

Adjuvants are central to the efficacy of subunit vaccines. Aluminum hydroxide (alum) is the most commonly used vaccine adjuvant, yet its adjuvanticity is often weak and mechanisms of triggering antibody responses remain poorly understood. We demonstrate that site-specific modification of immunogens with short peptides composed of repeating phosphoserine (pSer) residues enhances binding to alum and prolongs immunogen bioavailability. The pSer-modified immunogens formulated in alum elicited greatly increased germinal center, antibody, neutralizing antibody, memory and long-lived plasma cell responses compared to conventional alum-adsorbed immunogens. Mechanistically, pSer-immunogen:alum complexes form nanoparticles that traffic to lymph nodes and trigger B cell activation through multivalent and oriented antigen display. Direct uptake of antigen-decorated alum particles by B cells upregulated antigen processing and presentation pathways, further enhancing B cell activation. These data provide insights into mechanisms of action of alum and introduce a readily translatable approach to significantly improve humoral immunity to subunit vaccines using a clinical adjuvant.
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http://dx.doi.org/10.1038/s41591-020-0753-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069805PMC
March 2020

Relationship of obstructive sleep apnoea severity and subclinical systemic atherosclerosis.

Eur Respir J 2020 02 6;55(2). Epub 2020 Feb 6.

Institute for Human Genomic Study, College of Medicine, Korea University, Seoul, Republic of Korea

Obstructive sleep apnoea (OSA) is a common form of sleep disordered breathing. Untreated OSA might accelerate atherosclerosis, potentially increasing the cardiovascular disease burden in patients. The present study aimed to evaluate the association between objectively measured OSA severity and the presence of subclinical systemic atherosclerosis using noninvasive measurements, including tomographic quantification of the calcium burden.A total of 2157 participants of the Korean Genome and Epidemiology Study, who were free of structural heart disease and underwent both in-home polysomnography and chest computed tomography, were cross-sectionally analysed. Participants were divided into three groups based on the severity of OSA: no OSA (apnoea-hypopnoea index (AHI) <5 events·h, n=1096), mild OSA (AHI 5- <15 events·h, n=700) and moderate-to-severe OSA (AHI ≥15 events·h, n=361). Calcium deposits in the thoracic aorta and coronary arteries were measured by the Agatston score.Participants with moderate-to-severe OSA were 1.6 times (95% CI 1.18-2.15 times; p=0.002) more likely to have ascending thoracic aorta calcification (≥100 units) than those without OSA, after adjustment for cardiovascular risk factors. In addition, the association between moderate-to-severe OSA and ascending thoracic aorta calcification of subjects with higher epicardial fat volume was slightly stronger than that in patients without OSA and in the lowest epicardial fat volume tertile (OR 2.11, 95% CI 1.30-3.43).Severity of OSA in the general population was independently associated with subclinical systemic atherosclerosis. These findings highlight the potential importance of severe OSA, especially in subjects with higher epicardial fat, as a possible predictive factor for systemic atherosclerosis and cardiovascular disease.
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http://dx.doi.org/10.1183/13993003.00959-2019DOI Listing
February 2020

Excessive daytime sleepiness and topographic expansion of Lewy pathology.

Neurology 2019 10 30;93(15):e1425-e1432. Epub 2019 Aug 30.

From the Institute of Human Genomic Study (R.D.A., C.S.), Korea University College of Medicine, Ansan-si, Gyeonggi-do, South Korea; the Pacific Health Research and Education Institute (R.D.A., G.W.R., L.R.W., H.P.), Honolulu, HI; the Departments of Medicine (G.W.R.) and Pathology (J.H.U.-L.) and the John A. Hartford Foundation Center of Excellence in Geriatrics, Department of Geriatric Medicine (G.W.R., K.H.M., H.P.), John A. Burns School of Medicine, University of Hawaii, Honolulu; the Veterans Affairs Pacific Islands Health Care System (G.W.R., L.R.W., H.P.), Honolulu, HI; the Michael J. Crescenz Veterans Affairs Medical Center and the University of Pennsylvania Perelman School of Medicine (J.E.D.), Philadelphia; Kuakini Medical Center (K.H.M.), Honolulu, HI; the National Institute on Aging (L.J.L.), Bethesda, MD; and the San Francisco Veterans Affairs Medical Center and the Department of Neurology (C.M.T.), University of California-San Francisco.

Objective: While excessive daytime sleepiness (EDS) can predate the clinical diagnosis of Parkinson disease (PD), associations with underlying PD pathogenesis are unknown. Our objective is to determine if EDS is related to brain Lewy pathology (LP), a marker of PD pathogenesis, using clinical assessments of EDS with postmortem follow-up.

Methods: Identification of LP was based on staining for α-synuclein in multiple brain regions in a sample of 211 men. Data on EDS were collected at clinical examinations from 1991 to 1999 when participants were aged 72-97 years.

Results: Although EDS was more common in the presence vs absence of LP ( = 0.034), the association became stronger in neocortical regions. When LP was limited to the olfactory bulb, brainstem, and basal forebrain (Braak stages 1-4), frequency of EDS was 10% (4/40) vs 17.5% (20/114) in decedents without LP ( = 0.258). In contrast, compared to the absence of LP, EDS frequency doubled (36.7% [11/30], = 0.023) when LP reached the anterior cingulate gyrus, insula mesocortex, and midfrontal, midtemporal, and inferior parietal neocortex (Braak stage 5). With further infiltration into the primary motor and sensory neocortices (Braak stage 6), EDS frequency increased threefold (51.9% [14/27], < 0.001). Findings were similar across sleep-related features and persisted after adjustment for age and other covariates, including the removal of PD and dementia with Lewy bodies.

Conclusions: The association between EDS and PD includes relationships with extensive topographic LP expansion. The neocortex could be especially vulnerable to adverse relationships between sleep disorders and aggregation of misfolded α-synuclein and LP formation.
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http://dx.doi.org/10.1212/WNL.0000000000008241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010324PMC
October 2019

Efficacy of the Autoimmune Protocol Diet as Part of a Multi-disciplinary, Supported Lifestyle Intervention for Hashimoto's Thyroiditis.

Cureus 2019 Apr 27;11(4):e4556. Epub 2019 Apr 27.

Independent Researcher, Columbia, USA.

Background Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is an autoimmune disorder affecting the thyroid gland and is the most common cause of hypothyroidism in the US. Despite medical management with thyroid hormone replacement, many individuals with HT continue to experience symptoms and impaired quality of life. Given the limited number of efficacious treatments outside of hormone replacement and the overall burden of continued symptomatic disease, this pilot study was designed to determine the efficacy of a multi-disciplinary diet and lifestyle intervention for improving the quality of life, clinical symptom burden, and thyroid function in a population of middle-aged women with HT. Materials and methods The study recruited 17 normal or overweight (body mass index (BMI) <29.9) female subjects between the ages of 20 and 45 with a prior diagnosis of HT. The 17 women participated in a 10-week online health coaching program focused on the implementation of a phased elimination diet known as the Autoimmune Protocol (AIP). The 36-Item Short Form Health Survey (SF-36) and Cleveland Clinic Center for Functional Medicine's Medical Symptoms Questionnaire (MSQ) were used to measure the participant's health-related quality of life (HRQL) and clinical symptom burden, respectively, before and after the 10-week program. The participants completed serologic testing that included a complete blood cell count (CBC) with differential, complete metabolic profile (CMP), thyroid function tests, including thyroid stimulating hormone (TSH), total and free T4, and total and free T3, thyroid antibodies, including thyroid peroxidase antibodies (TPO) and anti-thyroglobulin antibodies (TGA), and high-sensitivity C-reactive protein (hs-CRP).  Results Sixteen women (n = 16) completed the SF-36 and MSQ before and after the 10-week program. There was a statistically significant improvement in HRQL as measured by all eight subscales of the SF-36 with the most marked improvements noted in the physical role functioning, emotional role functioning, vitality, and general health subscales. The clinical symptom burden, as measured by the MSQ, decreased significantly from an average of 92 (SD 25) prior to the program to 29 (SD 20) after the program. There were no statistically significant changes noted in any measure of thyroid function, including TSH, free and total T4, free and total T3 (n = 12), as well as thyroid antibodies (n = 14). Inflammation, as measured by hs-CRP (n = 14), was noted to significantly decrease by 29% (p = 0.0219) from an average of 1.63 mg/L (SD 1.72) pre-intervention to 1.15 mg/L (SD 1.31) post-intervention. Conclusions Our study suggests that an online diet and lifestyle program facilitated by a multi-disciplinary team can significantly improve HRQL and symptom burden in middle-aged female subjects with HT. While there were no statistically significant changes noted in thyroid function or thyroid antibodies, the study's findings suggest that AIP may decrease systemic inflammation and modulate the immune system as evidenced by a decrease in mean hs-CRP and changes in white blood cell (WBC) counts. Given the improvements seen in the HRQL and participants' symptom burden as well as markers of immune activity and inflammation, further studies in larger populations implementing AIP as part of a multi-disciplinary diet and lifestyle program are warranted.
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http://dx.doi.org/10.7759/cureus.4556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592837PMC
April 2019

Effects of Social Development Intervention in Childhood on Adult Life at Ages 30 to 39.

Prev Sci 2019 10;20(7):986-995

College of Education, University of Washington, Seattle, WA, USA.

Elementary schools can be effective sites for universal preventive interventions. Less is known about how long effects of intervention in elementary grades last. Can they improve outcomes in adulthood? To test effects of a social developmental intervention in the elementary grades on adult life through the 30s, the Seattle Social Development Project, a nonrandomized controlled trial, followed all consenting 5th-grade students (N = 808) from 18 Seattle public elementary schools from age 10 (in 1985) to age 39 (in 2014), with 88% retention. The sample was gender balanced and ethnically and economically diverse. The full intervention, called Raising Healthy Children, continued from Grades 1 through 6 and consisted of teacher in-service training in classroom management and instructional methods; cognitive, social, and refusal skills training for children; and parent workshops in child behavior monitoring and management, academic support, and anticipatory guidance. Using structural equation modeling, we examined intervention effects from age 30 to age 39 across 9 constructs indicating 3 domains of adult life: health behavior, positive functioning, and adult health and success. An omnibus test across all 9 constructs indicated a significant positive overall intervention-control difference. Examined individually, significant intervention effects included better health maintenance behavior, mental health, and overall adult health and success. Significant effects were not found on substance use disorder symptoms, sex-risk behaviors, or healthy close relationships in the 30s. Results indicate that sustained, theory-based, multicomponent intervention in the elementary grades can produce lasting changes in health maintenance, mental health, and adult functioning through the 30s.
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http://dx.doi.org/10.1007/s11121-019-01023-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722016PMC
October 2019

Online Writing Processes in Translating Cognition into Language and Transcribing Written Language by Stylus and Keyboard in Upper Elementary and Middle School Students With Persisting Dysgraphia or Dyslexia.

Learn Disabil 2018 ;23(2)

University of Washington, Measurement and Statistics.

Participants in this study completed an on-line experiment in which they wrote essays by stylus or keyboard. Three translation measures (length of language burst, length of pauses, and rate of pausing) and four transcription measures (total words, total time, words/minute, and percent spelling errors) for composition were analyzed for two research aims. Research Aim 1 addressed whether upper elementary and middle school students with carefully diagnosed transcription disabilities (dysgraphia with impaired handwriting, =18, or dyslexia with impaired spelling, =20) showed significant differences from pretest to posttest, across modes of transcription (stylus or keyboard), and between diagnostic groups. Results showed significant (a) change after intervention (18 computerized lessons with learning activities in letter formation/selection, spelling, and composing) in length of pauses, total time, and words per minute; (b) mode effects (fewer words and less time by stylus; fewer pauses per minute by keyboard); and (c) interactions with diagnostic group in response to intervention on some measures. Research Aim 2 addressed whether following intervention each of the diagnostic groups performed comparably to a typical control group (=15) in the same on-line experiment. Results showed (a) comparable performance of the dysgraphia and control groups on all keyboarding tasks but differences on two stylus measures; and (b) lack of comparable performance of the dyslexia and control groups on two stylus measures (total words and percent spelling errors) and the four keyboarding tasks related to transcription. Implications for assistive technology and writing instruction for dysgraphia and dyslexia are discussed.
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http://dx.doi.org/10.18666/LDMJ-2018-V23-I2-9008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380177PMC
January 2018

Association of brain heptachlor epoxide and other organochlorine compounds with lewy pathology.

Mov Disord 2019 02 30;34(2):228-235. Epub 2018 Dec 30.

Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii, USA.

Background: Organochlorine pesticides are associated with an increased risk of Parkinson's disease. A preliminary analysis from the Honolulu-Asia Aging Study suggested that heptachlor epoxide, a metabolite from an organochlorine pesticide extensively used in Hawaii, may be especially important. This was a cross sectional analysis to evaluate the association of heptachlor epoxide and other organochlorine compounds with Lewy pathology in an expanded survey of brain organochlorine residues from the longitudinal Honolulu-Asia Aging Study.

Methods: Organochlorines were measured in frozen occipital or temporal lobes in 705 brains using gas chromatography with mass spectrometry. Lewy pathology was identified using hematoxylin and eosin- and α-synuclein immunochemistry-stained sections from multiple brain regions.

Results: The prevalence of Lewy pathology was nearly doubled in the presence versus the absence of heptachlor epoxide (30.1% versus 16.3%, P < 0.001). Although associations with other compounds were weaker, hexachlorobenzene (P = 0.003) and α-chlordane (P = 0.007) were also related to Lewy pathology. Most of the latter associations, however, were a result of confounding from heptachlor epoxide. Neither compound was significantly related to Lewy pathology after adjustment for heptachlor epoxide. In contrast, the association of heptachlor epoxide with Lewy pathology remained significant after adjustments for hexachlorobenzene (P = 0.013) or α-chlordane (P = 0.005). Findings were unchanged after removal of cases of PD and adjustment for age and other characteristics.

Conclusions: Organochlorine pesticides are associated with the presence of Lewy pathology in the brain, even after exclusion of PD cases. Although most of the association is through heptachlor epoxide, the role of other organochlorine compounds is in need of clarification. © 2018 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602549PMC
February 2019

Behavioral and brain evidence for language by ear, mouth, eye, and hand and motor skills in literacy learning.

Int J Sch Educ Psychol 2019 15;7(Suppl 1):182-200. Epub 2018 Aug 15.

Educational Measurement and Statistics, University of Washington, Seattle, Washington, USA.

Two studies were conducted of students with and without persisting Specific Learning Disabilities (SLDs-WL) in Grades 4 to 9 (M = 11 years, 11 months) that supported the hypotheses that CELF 4 parent ratings for listening (language by ear), speaking (language by mouth), reading (language by eye), and writing (language by hand) were correlated with both (a) normed, standardized behavioral measures of listening, speaking, reading, and writing achievement (Study 1, 94 boys and 61 girls); and (b) fMRI connectivity or DTI white matter integrity involving brain regions for primary motor functions or motor planning and control, or motor timing in a subsample of right handers who did not wear metal (Study 2, 28 boys and 16 girls). Results of these assessment studies, which have implications for planning instruction for three SLDs-WL (dysgraphia, dyslexia, and oral and written language learning disability [OWL LD]), show that more than multisensory instruction is relevant. Language by ear, by mouth, by eye, and by hand, as well as motor planning, control, and output skills and motor timing should also be considered. Research is also reviewed that supports other processes beyond multisensory input alone that should also be considered for students with SLDs-WL.
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http://dx.doi.org/10.1080/21683603.2018.1458357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050657PMC
August 2018

Emotional and Behavioral Correlates of Persisting Specific Learning Disabilities in Written Language during Middle Childhood and Early Adolescence.

J Psychoeduc Assess 2018 Oct 27;36(7):651-669. Epub 2017 Mar 27.

University of Washington, Educational Psychology (Center for Oral and Written Language Learners OWLs).

Parents completed the while their children (94 boys, 61 girls; =11 years-11 months) were given tests. Evidence-based profiles of multiple test scores and history (emergence and persistence) were used to assign to groups without specific learning disabilities in written language (SLDs-WL) (= 42 control) or with SLDs-WL: (=29 dysgraphia, =65 dyslexia, or =19 oral and written language learning disability [OWL LD]). Parent ratings fell in the clinical or at risk ranges for some individuals in all groups, but mean ratings showed nine significant main effects for group (n=4): Behavioral Symptoms Index, Internalizing Problems Composite, Adaptive Skills Composite, two Clinical Scales (Atypicality and Attention Problems), and four Adaptive Scales (Adaptability, Activities of Daily Living, Leadership, and Functional Communication). Each SLDs-WL group differed significantly from the control group on these nine ratings, except dysgraphia on Atypicality and dyslexia on Adaptive Composite, Adaptability, and Leadership; and each correlated with one or more hallmark impairments associated with a specific SLD-WL. In an fMRI study (without OWL LD), the dysgraphia and dyslexia groups, but not control group, showed connectivity with amygdala; Internalizing Problems Composite (internal stress) correlated with amygdala connectivity from two cortical regions involved in written word processing and production for all groups (N=40). Applications to assessing emotional and behavioral correlates of SLDs-WL for educational services and future research are discussed.
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http://dx.doi.org/10.1177/0734282917698056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291223PMC
October 2018

When designing vaccines, consider the starting material: the human B cell repertoire.

Curr Opin Immunol 2018 08 3;53:209-216. Epub 2018 Sep 3.

Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Division of Infectious Diseases, Department of Medicine, UCSD School of Medicine, La Jolla, CA 92093, USA. Electronic address:

Most viral vaccines provide protection from infection through the generation of neutralizing antibodies (nAbs). The repertoire of B cells responding to immunization is the starting material from which nAbs eventually arise. Immunization strategies are increasingly targeting precise B cell specificities to mimic nAbs generated during natural infection, in an effort to maximize the potency of the vaccine-elicited Ab response. An understanding of the human B cell specificities capable of immunogen recognition can aid in immunogen design and inform decision-making for clinical advancement. Here, we review what is known about antigen-specific and epitope-specific naive B cell repertoires in humans and mice, and we consider the challenges for identifying and analyzing antigen-specific naive B cell repertoires. Finally, we provide a framework for further exploration, interpretation, utilization of the B cell repertoire to facilitate vaccine discovery.
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http://dx.doi.org/10.1016/j.coi.2018.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148213PMC
August 2018

Understanding Interest and Self-Efficacy in the Reading and Writing of Students with Persisting Specific Learning Disabilities during Middle Childhood and Early Adolescence.

Int J Educ Method 2017 Jul 15;3(1):41-64. Epub 2017 Jul 15.

University of Washington, USA.

Three methodological approaches were applied to understand the role of interest and self-efficacy in reading and/or writing in students without and with persisting specific learning disabilities (SLDs] in literacy. For each approach students in grades 4 to 9 completed a survey in which they rated 10 reading items and 10 writing items on a Scale 1 to 5; all items were the same but domain varied. The first approach applied Principal Component Analysis with Varimax Rotation to a sample that varied in specific kinds of literacy achievement. The second approach applied bidirectional multiple regressions in a sample of students with diagnosed SLDs-WL to (a) predict literacy achievement from ratings on interest and self-efficacy survey items; and (b) predict ratings on interest and self-efficacy survey items from literacy achievement. The third approach correlated ratings on the surveys with BOLD activation on an fMRI word reading/spelling task in a brain region associated with approach/avoidance and affect in a sample with diagnosed SLDs-WL. The first approach identified two components for the reading items (each correlated differently with reading skills) and two components for the writing items (each correlated differently with writing skills), but the components were not the same for both domains. Multiple regressions supported predicting interest and self-efficacy ratings from current reading achievement, rather than predicting reading achievement from interest and self-efficacy ratings, but also bidirectional relationships between interest or self-efficacy in writing and writing achievement. The third approach found negative correlations with amygdala connectivity for 2 reading items, but 5 positive and 2 negative correlations with amygdala connectivity for writing items; negative correlations may reflect avoidance and positive correlations approach. Collectively results show the relevance and domain-specificity of interest and self-efficacy in reading and writing for students with persisting SLDs in literacy.
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http://dx.doi.org/10.12973/ijem.3.1.41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100801PMC
July 2017

Effects of Omitting Non-confounding Predictors From General Relative-Risk Models for Binary Outcomes.

J Epidemiol 2019 Mar 11;29(3):116-122. Epub 2018 Aug 11.

Center for Epidemiologic Research in Asia, Shiga University of Medical Science.

Background: The effects, in terms of bias and precision, of omitting non-confounding predictive covariates from generalized linear models have been well studied, and it is known that such omission results in attenuation bias but increased precision with logistic regression. However, many epidemiologic risk analyses utilize alternative models that are not based on a linear predictor, and the effect of omitting non-confounding predictive covariates from such models has not been characterized.

Methods: We employed simulation to study the effects on risk estimation of omitting non-confounding predictive covariates from an excess relative risk (ERR) model and a general additive-multiplicative relative-risk mixture model for binary outcome data in a case-control setting. We also compared the results to the effects with ordinary logistic regression.

Results: For these commonly employed alternative relative-risk models, the bias was similar to that with logistic regression when the risk was small. More generally, the bias and standard error of the risk-parameter estimates demonstrated patterns that are similar to those with logistic regression, but with greater magnitude depending on the true value of the risk. The magnitude of bias and standard error had little relation to study size or underlying disease prevalence.

Conclusions: Prior conclusions regarding omitted covariates in logistic regression models can be qualitatively applied to the ERR and the general additive-multiplicative relative-risk mixture model without substantial change. Quantitatively, however, these alternative models may have slightly greater omitted-covariate bias, depending on the magnitude of the true risk being estimated.
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http://dx.doi.org/10.2188/jea.JE20170226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375815PMC
March 2019

International Comparison of Abdominal Fat Distribution Among Four Populations: The ERA-JUMP Study.

Metab Syndr Relat Disord 2018 05;16(4):166-173

3 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh , Pittsburgh, Pennsylvania.

Background: Abdominal fat distribution varies across groups with different races or environments. Whether environmental factors, apart from racial differences, affect abdominal fat distribution is unknown.

Methods: We compared the abdominal fat distribution of four groups; different races with similar environments (Caucasians vs. Japanese Americans), different environments with an identical race (Japanese Americans vs. Japanese), and similar races with similar environments (Japanese vs. Koreans). A population-based sample of 1212 men aged 40-49 were analyzed: 307 Caucasians and 300 Japanese Americans in the United States, 310 Japanese in Japan, and 295 Koreans in Korea. We compared the proportion of visceral adipose tissue area to total abdominal adipose tissue area (VAT%) and other factors that can affect abdominal fat distribution (smoking, alcohol use, physical activity levels, and metabolic factors).

Results: VAT% was significantly higher in Japanese and Koreans than in Japanese Americans and Caucasians (50.0, 48.5, 43.2, 41.0%, respectively, P < 0.001). Even after adjustment for possible confounders, the significant VAT% difference remained in comparing groups with identical race but different environments (i.e., Japanese vs. Japanese Americans). In contrast, comparing groups with different races but similar environments (i.e., Caucasians vs. Japanese Americans), VAT% was not significantly different. Comparing groups with similar races and similar environments (i.e., Japanese vs. Koreans), VAT% did not significantly differ.

Conclusions: Environmental differences, apart from racial differences, affect the difference in abdominal fat distribution across different groups in middle-aged men.
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http://dx.doi.org/10.1089/met.2017.0132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931176PMC
May 2018

Effective Instruction for Persisting Dyslexia in Upper Grades: Adding Hope Stories and Computer Coding to Explicit Literacy Instruction.

Educ Inf Technol (Dordr) 2018 May 20;23(3):1043-4068. Epub 2017 Sep 20.

Educational Psychology (Center for Oral and Written Language Learners OWLs), UW.

Children in grades 4 to 6 (=14) who despite early intervention had persisting dyslexia (impaired word reading and spelling) were assessed before and after computerized reading and writing instruction aimed at subword, word, and syntax skills shown in four prior studies to be effective for treating dyslexia. During the 12 two-hour sessions once a week after school they first completed HAWK Letters in Motion© for manuscript and cursive handwriting, HAWK Words in Motion© for phonological, orthographic, and morphological coding for word reading and spelling, and HAWK Minds in Motion© for sentence reading comprehension and written sentence composing. A reading comprehension activity in which sentences were presented one word at a time or one added word at a time was introduced. Next, to instill hope they could overcome their struggles with reading and spelling, they read and discussed stories about struggles of Buckminister Fuller who overcame early disabilities to make important contributions to society. Finally, they engaged in the new Kokopelli's World (KW)©, blocks-based online lessons, to learn computer coding in introductory programming by creating stories in sentence blocks (Tanimoto and Thompson 2016). Participants improved significantly in hallmark word decoding and spelling deficits of dyslexia, three syntax skills (oral construction, listening comprehension, and written composing), reading comprehension (with decoding as covariate), handwriting, orthographic and morphological coding, orthographic loop, and inhibition (focused attention). They answered more reading comprehension questions correctly when they had read sentences presented one word at a time (eliminating both regressions out and regressions in during saccades) than when presented one added word at a time (eliminating only regressions out during saccades). Indicators of improved self-efficacy that they could learn to read and write were observed. Reminders to pay attention and stay on task needed before adding computer coding were not needed after computer coding was added.
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http://dx.doi.org/10.1007/s10639-017-9647-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921925PMC
May 2018

Brain's functional network clustering coefficient changes in response to instruction (RTI) in students with and without reading disabilities: Multi-leveled reading brain's RTI.

Cogent Psychol 2018 9;5. Epub 2018 Jan 9.

Department of Radiology, Integrated Brain Imaging Center, University of Washington, Seattle, WA, USA.

In students in grades 4 to 9 (22 males, 20 females), two reading disability groups-dyslexia ( = 20) or oral and written language learning disability (OWL LD) ( = 6)-were compared to each other and two kinds of control groups-typical readers ( = 6) or dysgraphia ( = 10) on word reading/spelling skills and fMRI imaging before and after completing 18 computerized reading lessons. Mixed ANOVAs showed significant time effects on repeated measures within participants and between groups effects on three behavioral markers of reading disabilities-word reading/spelling: All groups improved on the three behavioral measures, but those without disabilities remained higher than those with reading disabilities. On fMRI reading tasks, analyzed for graph theory derived clustering coefficients within a neural network involved in cognitive control functions, on a task the time × group interaction was significant in right medial cingulate; on a task the time × group interaction was significant in left superior frontal and left inferior frontal gyri; and on a task the time × group interaction was significant in right middle frontal gyrus. Three white matter-gray matter correlations became significant only after reading instruction: axial diffusivity in left superior frontal region with right inferior frontal gyrus during ; mean diffusivity in left superior corona radiata with left middle frontal gyrus during ; and mean diffusivity in left anterior corona radiata with right middle frontal gyrus during . Significance of results for behavioral and brain response to reading instruction (RTI) is discussed.
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http://dx.doi.org/10.1080/23311908.2018.1424680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877472PMC
January 2018

Movement Issues Identified in Movement ABC2 Checklist Parent Ratings for Students with Persisting Dysgraphia, Dyslexia, and OWL LD and Typical Literacy Learners.

Learn Disabil (Pittsbg) 2018 ;23(1):10-23

Movement, which draws on motor skills and executive functions for managing them, plays an important role in literacy learning (e.g., movement of mouth during oral reading and movement of hand and fingers during writing); but relatively little research has focused on movement skills in students with specific learning disabilities as the current study did. Parents completed normed (ABC-2), ratings and their children in grades 4 to 9 ( = 11 years, 11 months; 94 boys, 61 girls) completed diagnostic assessment used to assign them to diagnostic groups: control typical language learning ( = 42), dysgraphia (impaired handwriting) ( = 29), dyslexia (impaired word decoding/reading and spelling) ( = 65), or oral and written language learning disability (OWL LD) (impaired syntax in oral and written language) ( = 19). The research aims were to (a) correlate the parent ratings for Scale A Static/Predictable Environment (15 items) and Scale B Dynamic/Unpredictable Environment (15 items) with reading and writing achievement in total sample varying within and across different skills; and (b) compare each specific learning disability group with the control group on parent ratings for Scale A, Scale B, and Scale C Movement-Related (Non-Motor Executive Functions, or Self-Efficacy, or Affect) (13 items). At least one parent rating was correlated with each assessed literacy achievement skill. Each of three specific learning disability groups differed from the control group on two Scale A (static/predictable environment) items (fastens buttons and forms letters with pencil or pen) and on three Scale C items (distractibility, overactive, and underestimates own ability); but only OWL LD differed from control on Scale B (dynamic/unpredictable environment) items. Applications of findings to assessment and instruction for students ascertained for and diagnosed with persisting specific learning disabilities in literacy learning, and future research directions are discussed.
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http://dx.doi.org/10.18666/LDMJ-2018-V23-I1-8449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872143PMC
January 2018