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The Southern dietary pattern, derived within the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, is characterized by high consumption of added fats, fried food, organ meats, processed meats, and sugar-sweetened beverages, and is associated with increased risk of several chronic diseases. The aim of the present study was to identify characteristics of individuals with high adherence to this dietary pattern.
We analyzed data from REGARDS, a national cohort of 30,239 black and white adults ≥ 45 years of age living in the US. Dietary data were collected using the Block 98 Food Frequency Questionnaire (FFQ). Multivariable linear regression was used to calculate standardized beta coefficients across all covariates for the entire sample and stratified by race and region.
We included 16,781 participants with complete dietary data. Among these, 34.6% were black, 45.6% male, 55.2% resided in stroke belt region, and the average age was 65 years. Black race was the factor with the largest magnitude of association to the Southern dietary pattern (Δ = 0.76 SD, p < 0.0001). Large differences in Southern dietary pattern adherence were observed between black participants and white participants in the stroke belt and non-belt (stroke belt Δ = 0.75 SD, non-belt Δ = 0.77 SD).
There was a high consumption of the Southern dietary pattern in the US black population, regardless of other factors, underlying our previous findings showing the substantial contribution of this dietary pattern to racial disparities in incident hypertension and stroke.
Antisaccade tasks can be used to index cognitive control processes, e.g. attention, behavioral inhibition, working memory, and goal maintenance in people with brain disorders. Though diagnoses of schizophrenia (SZ), schizoaffective (SAD), and bipolar I with psychosis (BDP) are typically considered to be distinct entities, previous work shows patterns of cognitive deficits differing in degree, rather than in kind, across these syndromes.
Large samples of individuals with psychotic disorders were recruited through the Bipolar-Schizophrenia Network on Intermediate Phenotypes 2 (B-SNIP2) study. Anti- and pro-saccade task performances were evaluated in 189 people with SZ, 185 people with SAD, 96 people with BDP, and 279 healthy comparison participants. Logistic functions were fitted to each group's antisaccade speed-performance tradeoff patterns.
Psychosis groups had higher antisaccade error rates than the healthy group, with SZ and SAD participants committing 2 times as many errors, and BDP participants committing 1.5 times as many errors. Latencies on correctly performed antisaccade trials in SZ and SAD were longer than in healthy participants, although error trial latencies were preserved. Parameters of speed-performance tradeoff functions indicated that compared to the healthy group, SZ and SAD groups had optimal performance characterized by more errors, as well as less benefit from prolonged response latencies. Prosaccade metrics did not differ between groups.
With basic prosaccade mechanisms intact, the higher speed-performance tradeoff cost for antisaccade performance in psychosis cases indicates a deficit that is specific to the higher-order cognitive aspects of saccade generation.
Previous research on the depression scale of the Patient Health Questionnaire (PHQ-9) has found that different latent factor models have maximized empirical measures of goodness-of-fit. The clinical relevance of these differences is unclear. We aimed to investigate whether depression screening accuracy may be improved by employing latent factor model-based scoring rather than sum scores.
We used an individual participant data meta-analysis (IPDMA) database compiled to assess the screening accuracy of the PHQ-9. We included studies that used the Structured Clinical Interview for DSM (SCID) as a reference standard and split those into calibration and validation datasets. In the calibration dataset, we estimated unidimensional, two-dimensional (separating cognitive/affective and somatic symptoms of depression), and bi-factor models, and the respective cut-offs to maximize combined sensitivity and specificity. In the validation dataset, we assessed the differences in (combined) sensitivity and specificity between the latent variable approaches and the optimal sum score (⩾10), using bootstrapping to estimate 95% confidence intervals for the differences.
The calibration dataset included 24 studies (4378 participants, 652 major depression cases); the validation dataset 17 studies (4252 participants, 568 cases). In the validation dataset, optimal cut-offs of the unidimensional, two-dimensional, and bi-factor models had higher sensitivity (by 0.036, 0.050, 0.049 points, respectively) but lower specificity (0.017, 0.026, 0.019, respectively) compared to the sum score cut-off of ⩾10.
In a comprehensive dataset of diagnostic studies, scoring using complex latent variable models do not improve screening accuracy of the PHQ-9 meaningfully as compared to the simple sum score approach.
Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.
Air pollution is linked to mortality and morbidity. Since humans spend nearly all their time indoors, improving indoor air quality (IAQ) is a compelling approach to mitigate air pollutant exposure. To assess interventions, relying on clinical outcomes may require prolonged follow-up, which hinders feasibility. Thus, identifying biomarkers that respond to changes in IAQ may be useful to assess the effectiveness of interventions.
We conducted a narrative review by searching several databases to identify studies published over the last decade that measured the response of blood, urine, and/or salivary biomarkers to variations (natural and intervention-induced) of changes in indoor air pollutant exposure.
Numerous studies reported on associations between IAQ exposures and biomarkers with heterogeneity across study designs and methods. This review summarizes the responses of 113 biomarkers described in 30 articles. The biomarkers which most frequently responded to variations in indoor air pollutant exposures were high sensitivity C-reactive protein (hsCRP), von Willebrand Factor (vWF), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 1-hydroxypyrene (1-OHP).
This review will guide the selection of biomarkers for translational studies evaluating the impact of indoor air pollutants on human health.
The relationship between nutrition and behavioural health (BH) outcomes has been established in the literature. However, the relationship between nutrition and anxiety is unclear. Furthermore, the relationship between nutrition and BH outcomes has not been examined in a US Army Soldier population. This study sought to understand the relationship between Soldiers’ nutritional intake and anxiety as well as depression.
This cross-sectional study utilised multivariable logistic regression analyses to examine the relationship between nutritional intake and BH outcomes.
The study utilised data collected in 2018 during a BH epidemiological consultation conducted at one Army installation.
Participants were 7043 US Army Soldiers at one Army installation.
Of the Soldiers completing the survey, 12 % (n 812) screened positive for anxiety and 11 % (n 774) for depression. The adjusted odds of anxiety were significantly higher among Soldiers who reported low fruit intake compared with Soldiers who reported high fruit intake (adjusted OR (AOR) 1·36; 95 % CI 1·04, 1·79). The adjusted odds of depression were higher for Soldiers who reported low fruit intake (AOR 1·35; 95 % CI 1·01, 1·79) and/or low green vegetable intake (AOR 1·37; 95 % CI 1·02, 1·83). Lastly, the adjusted odds of depression were lower for Soldiers who reported low sugary drink intake (AOR 0·62; 95 % CI 0·48, 0·81).
This study is the first to examine the important connection between nutritional intake and anxiety and depression at a US military installation. The information learned from this study has implications for enhancing Soldiers’ nutritional knowledge and BH, ultimately improving Soldiers’ health and medical readiness.
OBJECTIVES/GOALS: Breast cancer metastases are stochastic and difficult to detect. Therapy is often ineffective due to phenotypic changes of tumor cells at these sites. We engineered a synthetic metastatic niche to study the role of phenotypic transitions in the microenvironment on tumor cell phenotype. METHODS/STUDY POPULATION: The engineered metastatic niche is composed of a porous polycaprolactone scaffold implanted subcutaneously in Balb/c mice. The mice received an orthotopic inoculation of 4T1 cells (murine triple negative breast cancer) in the fourth right mammary fat pad and the disease was allowed to progress for 7-21 days (pre-metastatic to overt metastatic disease). The scaffolds and lungs (native metastatic site) were explanted and analyzed by single cell RNA-seq via Drop-seq. Cell phenotypes were identified and tracked over time with the Seurat and Monocle3 pipelines. Assessment of the impact of these cell populations on tumor cell phenotype was conducted through Transwell co-cultures. RESULTS/ANTICIPATED RESULTS: Healthy scaffolds are primarily composed of macrophages, dendritic cells, and fibroblasts – consistent with a foreign body response. Despite differences in the lung and scaffold prior to tumor inoculation, both tissues were marked by >5-fold increase in neutrophils/MDSCs. Additionally, 79% of genes at the scaffold that significantly changed over time were also identified in the lung, indicating key similarities in niche maturation. However, many immune cells at the scaffold had distinct phenotypes, with pro-inflammatory/cytotoxic characteristics. These changes clearly impacted tumor cell phenotype, as cells from the scaffold increased tumor cell migration and apoptosis in vitro. DISCUSSION/SIGNIFICANCE OF IMPACT: Early phenotypic changes at the engineered metastatic niche can identify signs of metastasis prior to colonization of tumor cells. Furthermore, dynamics of immune and stromal cells change throughout niche maturation, influencing tumor cell phenotype and may suggest targeted therapies. CONFLICT OF INTEREST DESCRIPTION: Lonnie Shea, Jacqueline Jeruss, and Grace Bushnell are named inventors on patents or patent applications.
‘Munchausen's syndrome by proxy’ characteristically describes women alleged to have fabricated or induced illnesses in children under their care, purportedly to attract attention. Where conclusive evidence exists the condition's aetiology remains speculative, where such evidence is lacking diagnosis hinges upon denial of wrong-doing (conduct also compatible with innocence). How might investigators obtain objective evidence of guilt or innocence? Here, we examine the case of a woman convicted of poisoning a child. She served a prison sentence but continues to profess her innocence. Using a modified fMRI protocol (previously published in 2001) we scanned the subject while she affirmed her account of events and that of her accusers. We hypothesized that she would exhibit longer response times in association with greater activation of ventrolateral prefrontal and anterior cingulate cortices when endorsing those statements she believed to be false (i.e., when she ‘lied’). The subject was scanned 4 times at 3 Tesla. Results revealed significantly longer response times and relatively greater activation of ventrolateral prefrontal and anterior cingulate cortices when she endorsed her accusers' version of events. Hence, while we have not ‘proven’ that this subject is innocent, we demonstrate that her behavioural and functional anatomical parameters behave as if she were.
Evidence suggests that healthy older adults with subjective memory complaints are at increased risk of dementia. Subjective Cognitive Impairment (SCI) may precede Mild Cognitive Impairment (MCI) in the clinical continuum of Alzheimer's disease (AD). Attentional deficits may be present early in AD, and associated functional changes have been reported in both MCI and AD. In the present study, activation during divided attention in SCI subjects was investigated using functional magnetic resonance imaging (fMRI). Additionally, amyloid uptake was investigated using 11C-PIB with positron emission tomography (PET).
Brain activation in 11 SCI subjects and 10 controls was compared during a divided attention task using fMRI. Additionally, five SCI subjects and 14 cognitively normal healthy controls underwent 11C-PIB PET scanning. Criteria for diagnosis of SCI were:
1. self-reported memory complaints,
2. objectively normal cognition on detailed neurocognitive testing,
3. absence of psychiatric or causative physical illness,
4. normal activities of daily living and
5. absence of MCI or dementia.
There were no differences in performance between SCI and control groups in terms of cognitive or behavioural measures. However, SCIs had increased activation in left medial temporal lobe, and bilateral thalamus, posterior cingulate and caudate. One SCI subject and one control subject had a pattern of 11C-PIB uptake similar to that seen in AD.
The activation changes identified in SCI may relate to compensatory increased activation in the face of early AD pathology. Larger, longitudinal studies are needed to determine the extent and significance of PIB uptake in SCI.
Depression is a major public health problem in European countries, and health systems need to ensure access to effective psychological and pharmacological treatments. Research suggests that improvements in depression care require “complex interventions” that implement change in several areas simultaneously.
We describe an observational study of the implementation of a “stepped care” model to provide care for all adults presenting with a new case of depression in a mixed urban-rural area of Scotland with a population of 76,000 people.
A team of 5.2 clinicians provided care for about 1,000 new cases of depression each year. “Guided Self-Help” was the baseline intervention for all patients, supplemented where necessary with pharmacological treatment and Cognitive Behavioural or Interpersonal Therapy.
Service delivery systems were reformed to provide: specialist treatment in primary care settings using primarily non-medical clinicians, comprehensive electronic clinical records, continuous outcome monitoring and intensive investment in staff training and support.
Clinical outcomes (measured by the Personal Health Questionnaire, Social and Work Adjustment Scale and EQ-5D) showed significant improvement despite relatively brief clinician contact (2.5 hours over 4.6 contacts). Savings of more than 50% were made on the antidepressant drug budget. Service user satisfaction ratings were high.
Population needs for depression care can be met using “stepped care” models such as that described above. A randomised controlled study of this approach would be required to fully test the model.
We show that the isomorphism problems for left distributive algebras, racks, quandles and kei are as complex as possible in the sense of Borel reducibility. These algebraic structures are important for their connections with the theory of knots, links and braids. In particular, Joyce showed that a quandle can be associated with any knot, and this serves as a complete invariant for tame knots. However, such a classification of tame knots heuristically seemed to be unsatisfactory, due to the apparent difficulty of the quandle isomorphism problem. Our result confirms this view, showing that, from a set-theoretic perspective, classifying tame knots by quandles replaces one problem with (a special case of) a much harder problem.
In this paper, we revisit our previous work in which we derive an effective macroscale description suitable to describe the growth of biological tissue within a porous tissue-engineering scaffold. The underlying tissue dynamics is described as a multiphase mixture, thereby naturally accommodating features such as interstitial growth and active cell motion. Via a linearization of the underlying multiphase model (whose nonlinearity poses a significant challenge for such analyses), we obtain, by means of multiple-scale homogenization, a simplified macroscale model that nevertheless retains explicit dependence on both the microscale scaffold structure and the tissue dynamics, via so-called unit-cell problems that provide permeability tensors to parameterize the macroscale description. In our previous work, the cell problems retain macroscale dependence, posing significant challenges for computational implementation of the eventual macroscopic model; here, we obtain a decoupled system whereby the quasi-steady cell problems may be solved separately from the macroscale description. Moreover, we indicate how the formulation is influenced by a set of alternative microscale boundary conditions.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Patients with congenital diaphragmatic hernias often have concomitant congenital heart disease (CHD), with small left-sided cardiac structures as a frequent finding. The goal of this study is to evaluate which left-sided heart structures are affected in neonates with congenital diaphragmatic hernias.
Retrospective review of neonates between May 2007 and April 2015 with a diagnosis of a congenital diaphragmatic hernia was performed. Clinical and echocardiographic data were extracted from the electronic medical record and indexed to body surface area and compared to normative values. Univariable regression models assessed for associations between different variables and length of stay.
Data of 52 patients showed decreased mean z scores for the LVIDd (–3.16), LVIDs (–3.05), aortic annulus (–1.68), aortic sinuses (–2.11), transverse arch (–3.11), and sinotubular junction (–1.47) with preservation of the aorta at the diaphragm compared to age-matched normative data with similar body surface areas. Regression analysis showed a percent reduction in length of stay per 1 mm size increase for LVIDd (8%), aortic annulus (27%), aortic sinuses (18%), sinotubular junctions (20%), and transverse arches (25%).
Patients with congenital diaphragmatic hernias have significantly smaller left-sided heart structures compared to age-matched normative data. Aortic preservation at the diaphragm provides evidence for a mass effect aetiology with increased right-to-left shunting at the fetal ductus resulting in decreased size. Additionally, length of stay appears to be prolonged with decreasing size of several of these structures. These data provide quantitative evidence of smaller left-sided heart structures in patients with congenital diaphragmatic hernias.
The mechanical properties of metallic glasses are often tuned by annealing, which influences these properties by adjusting the relaxation and/or crystallization status of the glasses. Here, we studied the hardness and modulus of Pt57.5Cu14.7Ni5.3P22.5 bulk metallic glass annealed at different temperatures by nanoindentation, where the annealing gives the material different fictive temperatures and fractions of crystallization. It is found that both reducing the fictive temperature of a fully amorphous sample and increasing the degree of crystallization in a partially crystallized sample increase hardness and modulus. Combining the two approaches, elevated hardness and modulus values are found for composite materials containing both crystalline and amorphous phases when they are compared to chemically identical alloys featuring similar percentages of crystalline and amorphous phases that have been prepared by annealing at higher temperatures. Our findings indicate that the mechanical properties of the platinum-based alloys can be customized by processing them with targeted heat treatments.
Energy-filtered transmission electron microscopy provides an opportunity to map the nanoscale elemental composition in polymeric systems. Nevertheless, it presents its own set of unique challenges in its application to soft materials. Here, we outline an optimized protocol for elemental mapping in soft materials using sulfur mapping of polymer/fullerene mixtures as an example. Three factors are crucial: (1) focusing at zero-loss, (2) using an objective aperture, and (3) maximizing signal-to-noise and counts for the chosen imaging conditions. Analyzing the corresponding source images, bright field images, and thickness maps can ensure optimum conditions are achieved for elemental mapping of polymers.