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Introduction: Fluorescence in situ hybridization (FISH) is currently the standard for diagnosing anaplastic lymphoma kinase (ALK)-rearranged (ALK+) lung cancers for ALK inhibitor therapies. ALK immunohistochemistry (IHC) may serve as a screening and alternative diagnostic method. The Canadian ALK (CALK) study was initiated to implement a multicenter optimization and standardization of laboratory developed ALK IHC and FISH tests across 14 hospitals., Methods: Twenty-eight lung adenocarcinomas with known ALK status were used as blinded study samples. Thirteen laboratories performed IHC using locally developed staining protocols for 5A4, ALK1, or D5F3 antibodies; results were assessed by H-score. Twelve centers conducted FISH using protocols based on Vysis' ALK break-apart FISH kit. Initial IHC results were used to optimize local IHC protocols, followed by a repeat IHC study to assess the results of standardization. Three laboratories conducted a prospective parallel IHC and FISH analysis on 411 consecutive clinical samples using post-validation optimized assays., Results: Among study samples, FISH demonstrated 22 consensus ALK+ and six ALK wild type tumors. Preoptimization IHC scores from 12 centers with 5A4 and the percent abnormal cells by FISH from 12 centers showed intraclass correlation coefficients of 0.83 and 0.68, respectively. IHC optimization improved the intraclass correlation coefficients to 0.94. Factors affecting FISH scoring and outliers were identified. Post-optimization concurrent IHC/FISH testing in 373 informative cases revealed 100% sensitivity and specificity for IHC versus FISH., Conclusions: Multicenter standardization study may accelerate the implementation of ALK testing protocols across a country/region. Our data support the use of an appropriately validated IHC assay to screen for ALK+ lung cancers.

Objective: Energy loss is a biomechanical parameter that represents the relative amount of energy absorbed by the aorta during the cardiac cycle. We aimed to correlate energy loss with ascending aortic aneurysm size and histopathologic findings to elucidate the pathophysiology of aneurysm complications., Methods: Aneurysmal ascending aortic specimens were obtained during surgery. Control specimens were obtained from autopsy and organ donors. Biaxial tensile tests were performed on the 4 quadrants of the aortic ring. Energy loss was calculated using the integral of the stress-strain curve during loading and unloading. It was compared with the size and the traditional biomechanical parameter, stiffness (apparent modulus of elasticity). Elastin, collagen, and mucopolysaccharide content were quantified using Movat pentachrome staining of histology slides., Results: A total of 41 aortas were collected (34 aneurysmal, 7 control). The aneurysms exhibited increased stiffness (P < .0001) and energy loss (P < .0001) compared with the controls. Energy loss correlated significantly with aortic size (P < .0001, r(2) = .60). A hinge point was noted at a diameter of 5.5 cm, after which energy loss increased rapidly. The relationship between energy loss and size became strongly linear once the size was indexed to the body surface area (P < .0001, r(2) = .78). Energy loss correlated with the histopathologic findings, especially the collagen/elastin ratio (P = .0002, r(2) = .49). High energy loss distinguished patients with pathologic histologic findings from others with similar diameters., Conclusions: As ascending aortas dilate, they exhibit greater energy loss that rapidly increases after 5.5 cm. This mirrors the increase in complications at this size. Energy loss correlates with imbalances in elastin and collagen composition, suggesting a measurable link between the histopathologic features and mechanical function., (Crown Copyright © 2014. Published by Mosby, Inc. All rights reserved.)

Cardiac inflammatory myofibroblastic tumor (IMT) is a rare entity affecting predominantly infants, children, and young adults. Although most tumors have a benign clinical course after complete surgical resection, some have significant clinical effects. We report the case of a 9-year-old girl who had sudden cardiac death as a result of occlusion of the left circumflex coronary artery. A review of 57 cases of cardiac IMTs reported in the literature in terms of epidemiology, clinical presentation, histologic and immunohistologic features, and outcome is presented. Recognition of this rare abnormality is important in order to initiate prompt surgical intervention.

Aim: There is a significant relationship between experiencing a severe mental illness, particularly psychosis, and exhibiting violent or offending behaviour. Reducing, if not preventing, the risks of violence among patients of mental health services is clinically warranted, but models to address this are limited., Methods: We provide a rationale for, and service description of, a pilot forensic satellite clinic embedded within an early intervention service for patients with emerging psychosis, mood disorder and/or personality disorders. The core elements of the programme and its implementation are described, and demographic, clinical and risk data are presented for the patients assessed during the clinic's pilot phase., Results: A total of 54 patients were referred, 45 of whom were subsequently assessed via primary or secondary consultation. The majority of patients were male, with psychosis (40%) or major depressive disorder (31%) as the most common diagnoses. Illicit substance use in the sample was common, as was previous aggression (81%) and prior criminal offences (51%). Most referrals related to assessing and managing violent behaviour (64%) and violent/homicidal ideation (38%). On the basis of the risk assessments, 71% of patients were rated as medium to high risk of offending., Conclusion: Assessing and managing risks of violent offending among young patients are both clinically indicated for a proportion of patients and feasible via a forensic outreach model. Given the proliferation of early psychosis services worldwide, the issue of managing, and ideally preventing, patient risk of violence will almost certainly have wide application. However, a comprehensive evaluation of this model is required to ultimately determine the effectiveness of this approach for improving patient outcomes., (© 2012 Wiley Publishing Asia Pty Ltd.)

Aims: The aims of this study were to determine the point prevalence of autism spectrum disorders and to estimate the prevalence of autistic traits in a youth mental health service., Methods: Following three educational sessions on autism spectrum disorders, treating clinicians were interviewed to determine whether the clients on their caseloads had (i) a confirmed prior diagnosis of autism spectrum disorder; (ii) were felt to exhibit autistic traits; or (iii) were not felt to exhibit autistic traits., Results: Information on autism spectrum disorder status was obtained for 476 patients. Of the included patients, 3.4% (n = 16) had a confirmed diagnosis of autism spectrum disorder and 7.8% (n = 37) were reported by treating clinicians to exhibit autistic traits., Conclusions: The rate of autism spectrum disorder was higher in this population than that in community samples with twice as many again being identified as having autistic traits by their treating clinicians. This has implications for correct diagnosis and appropriate management in these settings., (© 2011 Blackwell Publishing Asia Pty Ltd.)

Background: After 18 months of specialist care only about half of all first episode psychosis patients achieve functional recovery, and about 10-20% patients will not respond to initial treatment and have persistent psychotic symptoms. These patients need special attention in order to minimise the burden of disease and prolonged disability., Objective: This article reviews the management of young first episode psychosis patients with incomplete recovery, and focuses on the general practitioner's role, how to deal with treatment resistance, vocational rehabilitation, and other aspects of patient care., Discussion: Once the acute episode has been treated, it is important to avoid complacency and address other aspects contributing to a patient's wellbeing including social welfare, physical health and vocational rehabilitation. The prevention of relapse and the psychosocial development of the individual are key in fostering and promoting a healthy lifestyle, leading to improved quality of life. Treatment refractory patients need specialist care.

Background: A delay in the recognition of first episode psychosis is common and is often associated with psychological distress, social decline, and as recent evidence suggests, lasting brain changes. It is increasingly evident that early intervention potentially alters the course of these serious mental illnesses. General practitioners are ideally placed to identify early changes that may herald an emergent psychotic illness and to bridge the existing gap between patients, their families and specialist mental health services., Objective: This article summarises the rationale and importance of early detection of emerging psychotic illness in young people, and provides practical tips regarding its assessment and detection., Discussion: Early warning signs of emerging psychotic illnesses include behavioural, emotional and cognitive disturbances. Risk factors include a combination of a family history of a psychotic illness coupled with a decline in functioning, or a history of a brief self limiting psychotic episode (even if triggered by drugs such as cannabis or amphetamines). It is important that those working in primary care recognise these features in order to facilitate a speedy referral to specialist youth friendly mental health services, or if such services are not available, to initiate treatment and provide appropriate ongoing management.

Background: To optimise the management of emerging psychotic disorders in young people, close collaboration between the general practitioner and youth friendly specialist mental health services is favourable. Ideally, a multidisciplinary team including individual case management with expertise in early intervention should treat these patients for the initial 2-5 years. However, only a few areas across Australia currently provide this type of specialised service. Most GPs will at some point be faced with the reality of personally managing young patients with emerging psychotic disorders on their own, sometimes with very limited support., Objective: This article summarises key issues for the optimal management of emerging psychotic disorders, with a particular focus on the role of the GP., Discussion: Once an emerging psychotic disorder is confirmed, the engagement of the young person into therapy is the primary target. Ideally therapy integrates not only the patient, but also their family, carers and friends. General practitioners need to inform patients about the nature of the emerging psychotic illness, manage related comorbidities such as substance abuse, and initiate antipsychotic medication to avoid any unnecessary delay in resolution of symptoms. It is important to monitor the patient on a regular basis even after symptom recovery as up to 80% of cases that cease medication will relapse within 5 years.

Inflammatory cell infiltration and afferent neuropathy have been shown in the upper airway (UA) mucosa of subjects with obstructive sleep apnea (OSA). We hypothesized that inflammatory and denervation changes also involve the muscular layer of the pharynx in OSA. Morphometric analysis was performed on UA tissue from nonsnoring control subjects (n = 7) and patients with OSA (n = 11) following palatal surgery. As compared with control subjects, inflammatory cells were increased in the muscular layer of patients with OSA, with CD4+ and activated CD25+ T cells (both increased approximately threefold) predominating. Inflammation was also present in UA mucosa, but with a different pattern consisting of CD8+ (2.8-fold increase) and activated CD25+ (3.2-fold increase) T cell predominance. As ascertained by immunoreactivity for the panneuronal marker PGP9.5, there was a dramatic (5.7-fold) increase in intramuscular nerve fibers in OSA patients compared with control subjects, as well as direct evidence of denervation based on positive immunostaining of the muscle fiber sarcolemmal membrane for the neural cell adhesion molecule in patients with OSA. These data suggest that inflammatory cell infiltration and denervation changes affect not only the mucosa, but also the UA muscle of patients with OSA. This may have important implications for the ability to generate adequate muscular dilating forces during sleep.