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Conventional longitudinal behavioral genetic models estimate the relative contribution of genetic and environmental factors to stability and change of traits and behaviors. Longitudinal models rarely explain the processes that generate observed differences between genetically and socially related individuals. We propose that exchanges between individuals and their environments (i.e., phenotype–environment effects) can explain the emergence of observed differences over time. Phenotype–environment models, however, would require violation of the independence assumption of standard behavioral genetic models; that is, uncorrelated genetic and environmental factors. We review how specification of phenotype–environment effects contributes to understanding observed changes in genetic variability over time and longitudinal correlations among nonshared environmental factors. We then provide an example using 30 days of positive and negative affect scores from an all-female sample of twins. Results demonstrate that the phenotype–environment effects explain how heritability estimates fluctuate as well as how nonshared environmental factors persist over time. We discuss possible mechanisms underlying change in gene–environment correlation over time, the advantages and challenges of including gene–environment correlation in longitudinal twin models, and recommendations for future research.
To explore stakeholder perspectives regarding online diabetes nutrition education for American Indians and Alaska Natives (AI/AN) with type 2 diabetes (T2D).
Qualitative data were collected through focus groups and interviews. Focus group participants completed a brief demographic and internet use survey.
Focus groups and community participant interviews were conducted in diverse AI/AN communities. Interviews with nationally recognised content experts were held via teleconference.
Eight focus groups were conducted with AI/AN adults with T2D (n 29) and their family members (n 22). Community participant interviews were conducted with eleven clinicians and healthcare administrators working in Native communities. Interviews with nine content experts included clinicians and researchers serving AI/AN.
Qualitative content analysis used constant comparative method for coding and generating themes across transcripts. Descriptive statistics were computed from surveys. AI/AN adults access the internet primarily through smartphones, use the internet for many purposes and identify opportunities for online diabetes nutrition education.
Online diabetes nutrition education may be feasible in Indian Country. These findings will inform the development of an eLearning diabetes nutrition education programme for AI/AN adults with T2D.
In response to advancing clinical practice guidelines regarding concussion management, service members, like athletes, complete a baseline assessment prior to participating in high-risk activities. While several studies have established test stability in athletes, no investigation to date has examined the stability of baseline assessment scores in military cadets. The objective of this study was to assess the test–retest reliability of a baseline concussion test battery in cadets at U.S. Service Academies.
All cadets participating in the Concussion Assessment, Research, and Education (CARE) Consortium investigation completed a standard baseline battery that included memory, balance, symptom, and neurocognitive assessments. Annual baseline testing was completed during the first 3 years of the study. A two-way mixed-model analysis of variance (intraclass correlation coefficent (ICC)3,1) and Kappa statistics were used to assess the stability of the metrics at 1-year and 2-year time intervals.
ICC values for the 1-year test interval ranged from 0.28 to 0.67 and from 0.15 to 0.57 for the 2-year interval. Kappa values ranged from 0.16 to 0.21 for the 1-year interval and from 0.29 to 0.31 for the 2-year test interval. Across all measures, the observed effects were small, ranging from 0.01 to 0.44.
This investigation noted less than optimal reliability for the most common concussion baseline assessments. While none of the assessments met or exceeded the accepted clinical threshold, the effect sizes were relatively small suggesting an overlap in performance from year-to-year. As such, baseline assessments beyond the initial evaluation in cadets are not essential but could aid concussion diagnosis.
Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
This paper discusses the PhD research process from my perspective as an Aboriginal man. The paper illuminates how I navigated my way through a Western academic system using an Aboriginal framework. I give insights into the dynamics at play in both academic and traditional ways of knowing, being and doing. As an Aboriginal researcher, I was intent, as many Aboriginal scholars are, on doing research that was inclusive, respectful, culturally appropriate and satisfactory to both partners. The paper is not designed as a ‘one size fits all’, but may be used as a signpost for those who choose to do research with Aboriginal people or for insights into the experiences of an Aboriginal Higher Degree by Research student and researcher.
OBJECTIVES/SPECIFIC AIMS: The goals of our study are: (1) To test the hypothesis that the presence of any autoimmune cytopenia (ITP, AIHA, or ES) at time of cSLE diagnosis is associated with decreased risk of developing LN. (1b) To test the hypothesis that there is a lower risk of LN in patients with cSLE and any co-existing autoimmune cytopenia (ITP, AIHA, or ES) who had treatment with immunomodulatory or immunosuppressive therapy (intravenous immunoglobulin, corticosteroids, rituximab, or cyclophosphamide) before diagnosis of cSLE. (2) To test the hypothesis that in patients with cSLE who develop LN, the presence of any co-existing autoimmune cytopenia (ITP, AIHA, or ES) at time of cSLE diagnosis is associated with less severe LN. (3) To test the hypothesis that at the time of cSLE diagnosis, there is a lower incidence of double-stranded DNA (dsDNA) and a higher incidence of ribonucleoprotein autoantibodies in those with co-existing autoimmune cytopenias (ITP, AIHA, or ES). METHODS/STUDY POPULATION: This is a retrospective study of a large cohort of patients from the Emory Children’s Center, Children’s Healthcare of Atlanta (CHOA) satellite clinics and pediatric rheumatology inpatient services at any of the 3 CHOA hospitals (Egleston, Scottish Rite, and Hughes Spalding) with ICD 9 or ICD 10 codes corresponding to a diagnosis of SLE between January 1, 2000 and January 31, 2015. We will include patients diagnosed at age 2–16 years who meet at least 4 of the 11 American College of Rheumatology (ACR) classification criteria for SLE. We will consider these patients as having cSLE. We will exclude patients with less than 2 years of follow-up data and patients with a pre-existing diagnosis of cSLE who transferred care to our Emory/CHOA center. We will define time of diagnosis as time from initial evaluation for cSLE by a pediatric rheumatologist up to 28 days post cSLE diagnosis. We will define co-existing autoimmune cytopenia as preceding diagnosis of a primary autoimmune cytopenia or the presence of an autoimmune cytopenia at the time of initial evaluation for cSLE and up to 28 days post cSLE diagnosis. We will define AIHA as hemoglobin ≤10 g/dL with positive direct Coombs and/or reticulocytosis. We will define ITP as thrombocytopenia <100,000/mm3 and Evans syndrome as concurrent or sequential AIHA and ITP. We will define lupus nephritis (LN) as the presence of urine protein to creatinine ratio>0.5 in a patient with cSLE and/or biopsy demonstrating LN. IRB approval of the study protocol with waiver of informed consent has been obtained from the CHOA IRB. RESULTS/ANTICIPATED RESULTS: We have approximately 40 newly diagnosed cSLE patients annually; therefore, a study population of 400 patients with cSLE is possible. Therefore, assuming 50% of cSLE patients without autoimmune cytopenias have LN and 22% of cSLE patients with autoimmune cytopenias have LN, at an alpha of 0.05, we will have > 80% power to detect significant differences. We expect to show phenotypic differences in patients with co-existing autoimmune cytopenia and cSLE from other newly diagnosed cSLE patients. We expect that the presence of a co-existing autoimmune cytopenia and cSLE is associated with decreased risk of developing LN. We expect that there will be a decreased prevalence of LN in cSLE patients pretreated with immunosuppression further highlighting that earlier indicators of LN risk and early interventions are necessary. We expect to find decreased severity of LN in patients with a co-existing autoimmune cytopenia at time of cSLE diagnosis. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study will be conducted on one of the largest single-center cohorts of cSLE patients. We will determine whether pediatric patients with SLE and autoimmune cytopenias have a distinct clinical or serological phenotype and less severe disease. Our results will be significant in developing hypothesis for further retrospective or prospective multi-center or large database and immunological studies to understand the relationship of each individual autoimmune cytopenia to cSLE. It will provide the necessary background for further clinical and immunological studies to identify predictive biomarkers of cSLE severity.
We describe the use of implementation science at the unit level and organizational level to guide an intervention to reduce central-line–associated bloodstream infections (CLABSIs) in a high-volume, regional, burn intensive care unit (BICU).
A single center observational quasi-experimental study.
A regional BICU in Maryland serving 300–400 burn patients annually.
In 2011, an organizational-level and unit-level intervention was implemented to reduce the rates of CLABSI in a high-risk patient population in the BICU. At the organization level, leaders declared a goal of zero infections, created an infrastructure to support improvement efforts by creating a coordinating team, and engaged bedside staff. Performance data were transparently shared. At the unit level, the Comprehensive Unit-based Safety Program (CUSP)/ Translating Research Into Practice (TRIP) model was used. A series of interventions were implemented: development of new blood culture procurement criteria, implementation of chlorhexidine bathing and chlorhexidine dressings, use of alcohol impregnated caps, routine performance of root-cause analysis with executive engagement, and routine central venous catheter changes.
The use of an implementation science framework to guide multiple interventions resulted in the reduction of CLABSI rates from 15.5 per 1,000 central-line days to zero with a sustained rate of zero CLABSIs over 3 years (rate difference, 15.5; 95% confidence interval, 8.54–22.48).
CLABSIs in high-risk units may be preventable with the a use a structured organizational and unit-level paradigm.
Over two decades of astrometric and radial velocity data of short period stars at the Galactic center has the potential to provide unprecedented tests of General Relativity and insight into the astrophysics of the super-massive black hole. Fundamental to this is understanding the underlying statistical issues of fitting stellar orbits. Unintended prior effects can obscure actual physical effects from General Relativity and underlying extended mass distribution. At the heart of this is dealing with large parameter spaces inherent to multi-star fitting and ensuring acceptable coverage properties of the resulting confidence intervals in the Bayesian framework. This proceeding will detail some of the UCLA group's analysis and work in addressing these statistical issues.
In western Canada, more money is spent on wild oat herbicides than on any
other weed species, and wild oat resistance to herbicides is the most
widespread resistance issue. A direct-seeded field experiment was conducted
from 2010 to 2014 at eight Canadian sites to determine crop life cycle, crop
species, crop seeding rate, crop usage, and herbicide rate combination
effects on wild oat management and canola yield. Combining 2× seeding rates
of early-cut barley silage with 2× seeding rates of winter cereals and
excluding wild oat herbicides for 3 of 5 yr (2011 to 2013) often led to
similar wild oat density, aboveground wild oat biomass, wild oat seed
density in the soil, and canola yield as a repeated canola–wheat rotation
under a full wild oat herbicide rate regime. Wild oat was similarly well
managed after 3 yr of perennial alfalfa without wild oat herbicides.
Forgoing wild oat herbicides in only 2 of 5 yr from exclusively summer
annual crop rotations resulted in higher wild oat density, biomass, and seed
banks. Management systems that effectively combine diverse and optimal
cultural practices against weeds, and limit herbicide use, reduce selection
pressure for weed resistance to herbicides and prolong the utility of
threatened herbicide tools.
In the early 1950s, Lancefield divided streptococci into groups based on carbohydrates present in the cell wall and designated the groups A through H and K through T. In addition, streptococci may be classified by their characteristics on culture on sheep blood agar. β-Hemolytic streptococci produce zones of clear hemolysis around each colony; α-hemolytic streptococci (Streptococcus viridans) produce a green discoloration characteristic of incomplete hemolysis; absence of hemolysis is characteristic of γ-streptococci.
The sole member of Lancefield group A is Streptococcus pyogenes. Group A streptococcus is ubiquitous in the environment but with rare exceptions is exclusively found in or on the human host. About 5% to 20% of the population harbor group A streptococcus in their pharynx, and some are colonized on their skin. This organism produces a variety of suppurative infections; however, streptococcal pharyngitis, the most common, is characterized by the onset of sore throat, fever, painful swallowing, and chilliness. These symptoms combined with submandibular adenopathy, pharyngeal erythema, and exudates correlate with positive throat cultures in 85% to 90% of cases. Sore throat without fever or any of the other signs and symptoms has a low predictive value for pharyngitis caused by group A streptococcus. Rapid strep tests correlate with positive cultures in 68% to 99% of cases, but results depend greatly on the individual performing the test as well as the bacterial colony count. Colony counts greater than 100 per plate correlated with positive rapid strep tests in 95% of patients, and counts less than 100 per plate correlated with positive rapid strep tests for only 68% of patients.
Children with fetal alcohol spectrum disorders (FASD) show sociobehavioral impairments; however, the social cognitive profile contributing to these impairments is poorly understood. This study compared social perspective taking and empathy in children with FASD versus typically developing controls (TDC). Thirty-seven children with FASD and 21 TDC participated. Measures included parent-rated CBCL and SSIS, and NEPSY-II Theory of Mind, Test of Social Cognition and Index of Empathy. Parents rated the FASD group higher than TDC on indices of behavior problems and lower on indices of social skills and empathy. Children with FASD scored significantly below TDC on tasks requiring complex social cognition. The majority of correlations between social cognition and parent-ratings were not significant in FASD and TDC, with the exception of a negative correlation between self-reported empathy and parent-rated behavior difficulties in TDC. FASD subgroup analyses revealed lower theory of mind and empathy scores among children with ARND than pFAS/FAS. With regard to sex, males with FASD were rated as having more behavior difficulties than females, whereas TDC females obtained higher empathy ratings than males. In both groups, females scored higher on theory of mind and empathy indices. On theory of mind tasks, older children with FASD performed below younger, whereas younger TDC children performed more poorly than older. Children with FASD show reduced functioning on indices of sociobehavioral and social cognition, and the effects are influenced by sex and age. These findings provide insight into the clinical and social profile of children with FASD. (JINS, 2015, 21, 74–84)
Despite evidence for the effectiveness of structured psychological
therapies for bipolar disorder no psychological interventions have been
specifically designed to enhance personal recovery for individuals with
recent-onset bipolar disorder.
A pilot study to assess the feasibility and effectiveness of a new
intervention, recovery-focused cognitive–behavioural therapy (CBT),
designed in collaboration with individuals with recent-onset bipolar
disorder intended to improve clinical and personal recovery outcomes.
A single, blind randomised controlled trial compared treatment as usual
(TAU) with recovery-focused CBT plus TAU (n = 67).
Recruitment and follow-up rates within 10% of pre-planned targets to
12-month follow-up were achieved. An average of 14.15 h (s.d. = 4.21) of
recovery-focused CBT were attended out of a potential maximum of 18 h.
Compared with TAU, recovery-focused CBT significantly improved personal
recovery up to 12-month follow-up (Bipolar Recovery Questionnaire mean
score 310.87, 95% CI 75.00–546.74 (s.e. = 120.34), P =
0.010, d=0.62) and increased time to any mood relapse
during up to 15 months follow-up (χ2 = 7.64,
P<0.006, estimated hazard ratio (HR) = 0.38, 95%
CI 0.18–0.78). Groups did not differ with respect to medication
Recovery-focused CBT seems promising with respect to feasibility and
potential clinical effectiveness. Clinical- and cost-effectiveness now
need to be reliably estimated in a definitive trial.