Is Healthy Neuroticism Associated with Health Behaviors? A Coordinated Integrative Data Analysis.

Current literature suggests that neuroticism is positively associated with maladaptive life choices, likelihood of disease, and mortality. However, recent research has identified circumstances under which neuroticism is associated with positive outcomes. The current project examined whether "healthy neuroticism", defined as the interaction of neuroticism and conscientiousness, was associated with the following health behaviors: smoking, alcohol consumption, and physical activity. Using a pre-registered multi-study coordinated integrative data analysis (IDA) approach, we investigated whether "healthy neuroticism" predicted the odds of engaging in each of the aforementioned activities. Each study estimated identical models, using the same covariates and data transformations, enabling optimal comparability of results. These results were then meta-analyzed in order to estimate an average (N-weighted) effect and to ascertain the extent of heterogeneity in the effects. Overall, these results suggest that neuroticism alone was not related to health behaviors, while individuals higher in conscientiousness were less likely to be smokers or drinkers, and more likely to engage in physical activity. In terms of the healthy neuroticism interaction of neuroticism and conscientiousness, significant interactions for smoking and physical activity suggest that the association between neuroticism and health behaviors was smaller among those high in conscientiousness. These findings lend credence to the idea that healthy neuroticism may be linked to certain health behaviors and that these effects are generalizable across several heterogeneous samples.

[18F]fluoroethyltyrosine-induced Cerenkov Luminescence Improves Image-Guided Surgical Resection of Glioma.

The extent of surgical resection is significantly correlated with outcome in glioma; however, current intraoperative navigational tools are useful only in a subset of patients. We show here that a new optical intraoperative technique, Cerenkov luminescence imaging (CLI) following intravenous injection of O­(2-[18F]fluoroethyl)-L-tyrosine (FET), can be used to accurately delineate glioma margins, performing better than the current standard of fluorescence imaging with 5-aminolevulinic acid (5-ALA). Methods: Rats implanted orthotopically with U87, F98 and C6 glioblastoma cells were injected with FET and 5-aminolevulinic acid (5-ALA). Positive and negative tumor regions on histopathology were compared with CL and fluorescence images. The capability of FET CLI and 5-ALA fluorescence imaging to detect tumor was assessed using receptor operator characteristic curves and optimal thresholds (CLIOptROC and 5-ALAOptROC) separating tumor from healthy brain tissue were determined. These thresholds were used to guide prospective tumor resections, where the presence of tumor cells in the resected material and in the remaining brain were assessed by Ki-67 staining. Results: FET CLI signal was correlated with signal in preoperative PET images (y = 1.06x - 0.01; p < 0.0001) and with expression of the amino acid transporter SLC7A5 (LAT1). FET CLI (AUC = 97%) discriminated between glioblastoma and normal brain in human and rat orthografts more accurately than 5-ALA fluorescence (AUC = 91%), with a sensitivity >92% and specificity >91%, and resulted in a more complete tumor resection. Conclusion: FET CLI can be used to accurately delineate glioblastoma tumor margins, performing better than the current standard of fluorescence imaging following 5-ALA administration, and is therefore a promising technique for clinical translation.

Metabolic Imaging Detects Low Levels of Glycolytic Activity That Vary with Levels of c-Myc Expression in Patient-Derived Xenograft Models of Glioblastoma.

13C MRI of hyperpolarized [1-13C]pyruvate metabolism has been used in oncology to detect disease, investigate disease progression, and monitor response to treatment with a view to guiding treatment in individual patients. This technique has translated to the clinic with initial studies in prostate cancer. Here, we use the technique to investigate its potential uses in patients with glioblastoma (GB). We assessed the metabolism of hyperpolarized [1-13C]pyruvate in an orthotopically implanted cell line model (U87) of GB and in patient-derived tumors, where these were produced by orthotopic implantation of cells derived from different patients. Lactate labeling was higher in the U87 tumor when compared with patient-derived tumors, which displayed intertumoral heterogeneity, reflecting the intra- and intertumoral heterogeneity in the patients' tumors from which they were derived. Labeling in some patient-derived tumors could be observed before their appearance in morphologic images, whereas in other tumors it was not significantly greater than the surrounding brain. Increased lactate labeling in tumors correlated with c-Myc-driven expression of hexokinase 2, lactate dehydrogenase A, and the monocarboxylate transporters and was accompanied by increased radioresistance. Because c-Myc expression correlates with glioma grade, this study demonstrates that imaging with hyperpolarized [1-13C]pyruvate could be used clinically with patients with GB to determine disease prognosis, to detect early responses to drugs that modulate c-Myc expression, and to select tumors, and regions of tumors for increased radiotherapy dose.Significance: Metabolic imaging with hyperpolarized [1-13C]pyruvate detects low levels of c-Myc-driven glycolysis in patient-derived glioblastoma models, which, when translated to the clinic, could be used to detect occult disease, determine disease prognosis, and target radiotherapy. Cancer Res; 78(18); 5408-18. ©2018 AACR.

Investigating diagnostic bias in autism spectrum conditions: An item response theory analysis of sex bias in the AQ-10.

Diagnostic bias is a concern in autism spectrum conditions (ASC) where prevalence and presentation differ by sex. To ensure that females with ASC are not under-identified, it is important that ASC screening tools do not systematically underestimate autistic traits in females relative to males. We evaluated whether the AQ-10, a brief screen for ASC recommended by the National Institute of Clinical Excellence in cases of suspected ASC, exhibits such a bias. Using an item response theory approach, we evaluated differential item functioning and differential test functioning. We found that although individual items showed some sex bias, these biases at times favored males and at other times favored females. Thus, at the level of test scores the item-level biases cancelled out to give an unbiased overall score. Results support the continued use of the AQ-10 sum score in its current form; however, suggest that caution should be exercised when interpreting responses to individual items. The nature of the item level biases could serve as a guide for future research into how ASC affects males and females differently. Autism Res 2017, 10: 790-800. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

An analysis of differential item functioning by gender in the Learning Disability Screening Questionnaire (LDSQ).

The Learning Disability Screening Questionnaire (LDSQ; McKenzie & Paxton, 2006) was developed as a brief screen for intellectual disability. Although several previous studies have evaluated the LDSQ with respect to its utility as a clinical and research tool, no studies have considered the fairness of the test across males and females. In the current study we, therefore, used a multi-group item response theory approach to assess differential item functioning across gender in a sample of 211 males and 132 females assessed in clinical and forensic settings. Although the test did not show evidence of differential item functioning by gender, it was necessary to exclude one item due to estimation problems and to combine two very highly related items (concerning reading and writing ability) into a single literacy item Thus, in addition to being generally supportive of the utility of the LDSQ, our results also highlight possible areas of weakness in the tool and suggest possible amendments that could be made to test content to improve the test in future revisions.

Personality, health, and brain integrity: the Lothian birth cohort study 1936.

OBJECTIVE: To explore associations between the 5-factor model (FFM; neuroticism, extraversion, openness/intellect, agreeableness, and conscientiousness), personality traits, and measures of whole-brain integrity in a large sample of older people, and to test whether these associations are mediated by health-related behaviors. METHOD: Participants from the Lothian Birth Cohort 1936 completed the International Personality Item Pool measure, a 5-factor public-domain personality measure (http://ipip.ori.org), and underwent a structural magnetic resonance brain scan at the mean age of 73 years, yielding 3 measures of whole brain integrity: average white matter fractional anisotropy (FA), brain-tissue loss, and white matter hyperintensities (N = 529 to 565). Correlational and mediation analyses were used to test the potential mediating effects of health-related behaviors on the associations between personality and integrity. RESULTS: Lower conscientiousness was consistently associated with brain-tissue loss (ß = -0.11, p < 0.01), lower FA (ß = 0.16, p < 0.001) and white matter hyperintensities (ß = -0.10, p < 0.05). Smoking, alcohol consumption, diet, physical activity, body mass index and a composite health-behavior variable displayed significant associations with measures of brain integrity (range of r = 0.10 to 0.25). The direct effects of conscientiousness on brain integrity were mediated to some degree by health behaviors, with the proportions of explained direct effects ranging from 0.1% to 13.7%. CONCLUSION: Conscientiousness was associated with all 3 measures of brain integrity, which we tentatively interpret as the effects of personality on brain aging. Small proportions of the direct effects were mediated by individual health behaviors. RESULTS provide initial indications that lifetime stable personality traits may influence brain health in later life through health-promoting behaviors.

Estimating the level of functional ability of children identified as likely to have an intellectual disability.

Screening tools can provide an indication of whether a child may have an intellectual disability (ID). Item response theory (IRT) analyses can be used to assess whether the statistical properties of the tools are such that their utility extends beyond their use as a screen for ID. We used non-parametric IRT scaling analyses to investigate whether the Child and Adolescent Intellectual Disability Screening Questionnaire (CAIDS-Q) possessed the statistical properties that would suggest its use could be extended to estimate levels of functional ability and to estimate which (if any) features associated with intellectual impairment are consistently indicative of lower or higher levels of functional ability. The validity of the two proposed applications was assessed by evaluating whether the CAIDS-Q conformed to the properties of the Monotone Homogeneity Model (MHM), characterised by uni-dimensionality, local independence and latent monotonicity and the Double Monotone Model (DMM), characterised by the assumptions of the MHM and, in addition, of non-intersecting item response functions. We analysed these models using CAIDS-Q data from 319 people referred to child clinical services. Of these, 148 had a diagnosis of ID. The CAIDS-Q was found to conform to the properties of the MHM but not the DMM. In practice, this means that the CAIDS-Q total scores can be used to quickly estimate the level of a person's functional ability. However, items of the CAIDS-Q did not show invariant item ordering, precluding the use of individual items in isolation as accurate indices of a person's level of functional ability.

Modeling multisystem biological risk in later life: allostatic load in the Lothian birth cohort study 1936.

OBJECTIVES: To investigate and replicate a multisystem model of biological risk, or allostatic load, in a sample of generally healthy older adults. METHODS: Multigroup confirmatory factor analysis (MG-CFA) was applied to data from the Lothian Birth Cohort 1936 (n = 726). Blood samples were taken at a physical examination. Three markers of inflammation (fibrinogen, interleukin-6, and C-reactive protein), five metabolic markers (high- and low-density lipoprotein, body mass index, glycated hemoglobin, and triglyceride), and blood pressure (mean sitting systolic and diastolic blood pressure) were used to estimate a second-order CFA model of allostatic load. Our sample was split into those taking antihypertensive, anti-inflammatory, lipid-lowering, and diabetes medications (n = 470), and those who were not (n = 256), in order to test the stability of the CFA model across groups. RESULTS: In the nonmedicated sample, a second-order allostatic load model showed good fit to the data. However, the second-order model failed to estimate in the medicated group. The factor correlations between blood pressure and inflammation and metabolism were smaller in magnitude in the medicated group. Invariance analysis on the first-order measurement model suggested significant differences across groups in the associations of low-density lipoprotein and HbA1c with metabolism. CONCLUSIONS: Reliable measurement of allostatic load is possible in ageing samples free of medications but is complicated in the presence of medications. MG-CFA represents a highly versatile method for the analysis of allostatic load.

Brief report: an evaluation of the AQ-10 as a brief screening instrument for ASD in adults.

There is a need for brief screening instruments for autistic spectrum disorders (ASD) that can be used by frontline healthcare professionals to aid in the decision as to whether an individual should be referred for a full diagnostic assessment. In this study we evaluated the ability of a short form of the autism spectrum quotient (AQ) questionnaire, the 10 item AQ-10, to correctly classify individuals as having or not having ASD. In a sample of 149 individuals with ASD and 134 controls without an ASD diagnosis, we found that the full AQ (AQ-50) abridged AQ (AQ-S) and AQ-10 all performed well as a screen for ASD. ROC analysis indicated that sensitivity, specificity and area under the curve were very similar at suggested cut-off's for ASD across measures, with little difference in performance between the AQ-10 and full AQ-50. Results indicate the potential usefulness of the AQ-10 as a brief screen for ASD.