Behavioral inhibition in childhood predicts smaller hippocampal volume in adolescent offspring of parents with panic disorder.

Behavioral inhibition (BI) is a genetically influenced behavioral profile seen in 15-20% of 2-year-old children. Children with BI are timid with people, objects and situations that are novel or unfamiliar, and are more reactive physiologically to these challenges as evidenced by higher heart rate, pupillary dilation, vocal cord tension and higher levels of cortisol. BI predisposes to the later development of anxiety, depression and substance abuse. Reduced hippocampal volumes have been observed in anxiety disorders, depression and posttraumatic stress disorder. Animal models have demonstrated that chronic stress can damage the hippocampal formation and implicated cortisol in these effects. We, therefore, hypothesized that the hippocampi of late adolescents who had been behaviorally inhibited as children would be smaller compared with those who had not been inhibited. Hippocampal volume was measured with high-resolution structural magnetic resonance imaging in 43 females and 40 males at 17 years of age who were determined to be BI+ or BI- based on behaviors observed in the laboratory as young children. BI in childhood predicted reduced hippocampal volumes in the adolescents who were offspring of parents with panic disorder, or panic disorder with comorbid major depression. We discuss genetic and environmental factors emanating from both child and parent that may explain these findings. To the best of our knowledge, this is the first study to demonstrate a relationship between the most extensively studied form of temperamentally based human trait anxiety, BI, and hippocampal structure. The reduction in hippocampal volume, as reported by us, suggests a role for the hippocampus in human trait anxiety and anxiety disorder that warrants further investigation.

Comparison of CE-FDG-PET/CT with CE-FDG-PET/MR in the evaluation of osseous metastases in breast cancer patients.

BACKGROUND: Despite improvements in treatments, metastatic breast cancer remains difficult to cure. Bones constitute the most common site of first-time recurrence, occurring in 40-75% of cases. Therefore, evaluation for possible osseous metastases is crucial. Technetium 99 ((99)Tc) bone scintigraphy and fluorodexossyglucose (FDG) positron emission tomography (PET)-computed tomography (PET-CT) are the most commonly used techniques to assess osseous metastasis. PET magnetic resonance (PET-MR) imaging is an innovative technique still under investigation. We compared the capability of PET-MR to that of same-day PET-CT to assess osseous metastases in patients with breast cancer. METHODS: One hundred and nine patients with breast cancer, who underwent same-day contrast enhanced (CE)-PET-CT and CE-PET-MR, were evaluated. CE-PET-CT and CE-PET-MR studies were interpreted by consensus by a radiologist and a nuclear medicine physician. Correlations with prior imaging and follow-up studies were used as the reference standard. Binomial confidence intervals and a χ(2) test were used for categorical data, and paired t-test was used for the SUVmax data; a non-informative prior Bayesian approach was used to estimate and compare the specificities. RESULTS: Osseous metastases affected 25 out 109 patients. Metastases were demonstrated by CE-PET-CT in 22 out of 25 patients (88%±7%), and by CE-PET-MR in 25 out of 25 patients (100%). CE-PET-CT revealed 90 osseous metastases and CE-PET-MR revealed 141 osseous metastases (P<0.001). The estimated sensitivity of CE-PET-CT and CE-PET-MR were 0.8519 and 0.9630, respectively. The estimated specificity for CE-FDG-PET-MR was 0.9884. The specificity of CE-PET-CT cannot be determined from patient-level data, because CE-PET-CT yielded a false-positive lesion in a patient who also had other, true metastases. CONCLUSIONS: CE-PET-MR detected a higher number of osseous metastases than did same-day CE-PET-CT, and was positive for 12% of the patients deemed osseous metastasis-negative on the basis of CE-PET-CT.

Imaging appearance of the lateral rectus-superior rectus band in 100 consecutive patients without strabismus.

BACKGROUND AND PURPOSE: The lateral rectus-superior rectus band is an orbital connective tissue structure that has been implicated in a form of strabismus termed sagging eye syndrome. Our purpose was to define the normal MR imaging and CT appearance of this band in patients without strabismus. MATERIALS AND METHODS: Orbital MR imaging and CT examinations in 100 consecutive patients without strabismus were evaluated. Readers graded the visibility of the lateral rectus-superior rectus band on coronal T1WI, coronal STIR, and coronal CT images. Readers determined whether the band demonstrated superotemporal bowing or any discontinuities and whether a distinct lateral levator aponeurosis was seen. Reader agreement was assessed by κ coefficients. Association between imaging metrics and patient age/sex was calculated by using the Fisher exact test. RESULTS: The lateral rectus-superior rectus band was visible in 95% of coronal T1WI, 68% of coronal STIR sequences, and 70% of coronal CT scans. Ninety-five percent of these bands were seen as a continuous, arc-like structure extending from the superior rectus/levator palpebrae muscle complex to the lateral rectus muscle; 24% demonstrated superotemporal bowing; and in 82% of orbits, a distinct lateral levator aponeurosis was visible. Increasing patient age was negatively associated with lateral rectus-superior rectus band visibility (P=.03), positively associated with lateral rectus-superior rectus band superotemporal bowing (P=.03), and positively associated with lateral levator aponeurosis visibility (P=.01). CONCLUSIONS: The lateral rectus-superior rectus band is visible in most patients without strabismus on coronal T1WI. The age effect with respect to its visibility and superotemporal bowing could represent age-related connective tissue degeneration.

Neuroanatomic correlates of stroke-related myocardial injury.

BACKGROUND: Myocardial injury can occur after ischemic stroke in the absence of primary cardiac causes. The neuroanatomic basis of stroke-related myocardial injury is not well understood. OBJECTIVE: To identify regions of brain infarction associated with myocardial injury using a method free of the bias of an a priori hypothesis as to any specific location. METHODS: Of 738 consecutive patients with acute ischemic stroke, the authors identified 50 patients in whom serum cardiac troponin T (cTnT) elevation occurred in the absence of any apparent cause within 3 days of symptom onset. Fifty randomly selected, age- and sex-matched patients with ischemic stroke without cTnT elevation served as controls. Diffusion-weighted images with outlines of infarction were co-registered to a template, averaged, and then subtracted to find voxels that differed between the two groups. Voxel-wise p values were determined using a nonparametric permutation test to identify specific regions of infarction that were associated with cTnT elevation. RESULTS: The study groups were well balanced with respect to stroke risk factors, history of coronary artery disease, infarction volume, and frequency of right and left middle cerebral artery territory involvement. Brain regions that were a priori associated with cTnT elevation included the right posterior, superior, and medial insula and the right inferior parietal lobule. Among patients with right middle cerebral artery infarction, the insular cluster was involved in 88% of patients with and 33% without cTnT elevation (odds ratio: 15.00; 95% CI: 2.65 to 84.79). CONCLUSIONS: Infarctions in specific brain regions including the right insula are associated with elevated serum cardiac troponin T level indicative of myocardial injury.

Case clustering in infective endocarditis: the role of availability bias.

Limited data exist regarding the impact of variations in clinical practice and physicians' cognitive bias on the diagnosis of infective endocarditis (IE). As an illustration of these effects, unexpected clustering of IE diagnosis was encountered in a prospectively studied cohort. Transoesophageal echocardiography examinations for suspected IE were performed more frequently following a diagnosis of IE, and were associated with a subsequent cluster of IE cases. The cognitive bias of physicians resulting from a recent case of IE can lead to a transient increase in diagnosing additional cases of IE.

fMRI of sensitization to angry faces.

This study examined what is communicated by facial expressions of anger and mapped the neural substrates, evaluating the motivational salience of these stimuli. During functional magnetic resonance imaging, angry and neutral faces were presented to human subjects. Across experimental runs, signal adaptation was observed. Whereas fearful faces have reproducibly evoked response habituation in amygdala and prefrontal cortex, angry faces evoked sensitization in the insula, cingulate, thalamus, basal ganglia, and hippocampus. Complementary offline rating and keypress experiments determined an aversive rank ordering of angry, fearful, neutral, and happy faces and revealed behavioral sensitization to the angry faces. Subjects rated angry faces, in contrast to other face categories such as fear, as significantly more likely to directly inflict harm. Furthermore, they rated angry faces as significantly less likely to produce positive emotional outcomes than the other face categories. Together these data argue that angry faces, a directly aversive stimulus, produce a sensitization response.

The influence of gender on survival and tumor recurrence following adjuvant therapy of completely resected stages II and IIIa non-small cell lung cancer.

This study evaluates the influence of gender on survival and tumor recurrence following adjuvant therapy of completely resected stages II and IIIa non-small cell lung cancer (NSCLC). The Eastern Cooperative Oncology Group conducted a randomized prospective trial of adjuvant therapy in patients with completely resected stages II and IIIa NSCLC. A laboratory correlative study assessed the prevalence and prognostic significance of p53 and K-ras mutations. Patients were randomized to receive either radiotherapy (RT) alone or four cycles of cisplatin and VP-16 administered concurrently with radiotherapy (CRT). Median survival was 35 months for the 285 men and 41 months for the 203 women enrolled in the study (P = 0.12). The relative risk (RR) of death for men vs women was 1.19 (95% confidence interval [CI], 0.95-1.49). Median survival of the 147 men and 95 women randomized to the RT arm was 39 months each (P = 0.35). Median survival of the 138 men and 108 women randomized to the CRT arm was 30 and 42 months, respectively (P = 0.18). Disease recurrence patterns were similar between the genders. Univariate and multivariate analyses demonstrated improved survival for women with tumors of non-squamous histology (P < 0.01). The distribution of p53 and K-ras mutations was similar between the genders and had no influence on survival. Gender does not influence survival following adjuvant RT or CRT administered to patients with completely resected stages II and IIIa NSCLC. However, women with non-squamous histology have increased survival when compared to men.

An Approach to Combining Results From Multiple Methods Motivated by the ISO GUM.

The problem of determining a consensus value and its uncertainty from the results of multiple methods or laboratories is discussed. Desirable criteria of a solution are presented. A solution motivated by the ISO Guide to the Expression of Uncertainty in Measurement (ISO GUM) is introduced and applied in a detailed worked example. A Bayesian hierarchical model motivated by the proposed solution is presented and compared to the solution.

Maximum likelihood analysis for heteroscedastic one-way random effects ANOVA in interlaboratory studies.

This article presents results for the maximum likelihood analysis of several groups of measurements made on the same quantity. Following Cochran (1937, Journal of the Royal Statistical Society 4(Supple), 102-118; 1954, Biometrics 10, 101-129; 1980, in Proceedings of the 25th Conference on the Design of Experiments in Army Research, Development and Testing, 21-33) and others, this problem is formulated as a one-way unbalanced random-effects ANOVA with unequal within-group variances. A reparametrization of the likelihood leads to simplified computations, easier identification and interpretation of multimodality of the likelihood, and (through a non-informative-prior Bayesian approach) approximate confidence regions for the mean and between-group variance.