Rasch Measurement Theory's contribution to the psychometric properties of a co-created measure of health and wellness for Indigenous children and youth.

Objectives: To determine how Rasch Measurement Theory (RMT) methods can be used to assess the psychometric properties of the Aaniish Naa Gegii: the Children's Health and Wellbeing Measure (ACHWM) and Qanuippit.

Study Design And Setting: Indigenous children aged 8-18 years, from five communities, completed the 62-item ACHWM. We applied RMT methods to ACHWM data from 401 children (mean age 13.

The Transcriptomic Landscape of Prostate Cancer Development and Progression: An Integrative Analysis.

Next-generation sequencing of primary tumors is now standard for transcriptomic studies, but microarray-based data still constitute the majority of available information on other clinically valuable samples, including archive material. Using prostate cancer (PC) as a model, we developed a robust analytical framework to integrate data across different technical platforms and disease subtypes to connect distinct disease stages and reveal potentially relevant genes not identifiable from single studies alone. We reconstructed the molecular profile of PC to yield the first comprehensive insight into its development, by tracking changes in mRNA levels from normal prostate to high-grade prostatic intraepithelial neoplasia, and metastatic disease.

Fluorescence In Situ Hybridization and Rehybridization Using Bacterial Artificial Chromosome Probes.

Fluorescence in situ hybridization (FISH) method enables in situ genetic analysis of both metaphase and interphase cells from different types of material, including cell lines, cell smears, and fresh and paraffin-embedded tissue. Despite the growing number of commercially available FISH probes, still for large number of gene loci or chromosomal regions commercial probes are not available. Here we describe a simple method for generating FISH probes using bacterial artificial chromosomes (BAC).

The Isolation and Analysis of Circulating Tumor Cells.

Circulating tumor cells (CTCs), with their close association with cancer metastasis, the most aggressive feature of solid tumors, represent an important aspect of "liquid biopsy," which provides minimally- or noninvasive approaches for cancer detection and disease status monitoring. CTC analysis has shown the potential clinical applications in several cancer types and has been approved by FDA for clinical use in advanced breast, prostate, and colorectal cancer prognosis. In this chapter, we describe a CTC isolation method using a cell size and deformability-based system, Parsortix, and the immunofluorescence staining method to detect CTCs with both epithelial and mesenchymal features.

The potential of brentuximab vedotin, alone or in combination with current clinical therapies, in the treatment of testicular germ cell tumors.

Testicular germ cell tumors (TGCTs) are the commonest tumors in young men. With the advancement of chemotherapies, most TGCTs are successfully cured, even when diagnosed at an advanced and metastatic stage. However, a proportion of often young patients, median age 35-40, with advanced disease are not cured and will inevitably die.

Improving Prediction of Risk of Admission to Long-Term Care or Mortality Among Home Care Users With IDD.

Background: Frailty is an established predictor of admission into long-term care (LTC) and mortality in the elderly population. Assessment of frailty among adults with intellectual and developmental disabilities (IDD) using a generic frailty marker may not be as predictive, as some lifelong disabilities associated with IDD may be interpreted as a sign of frailty. This study set out to determine if adding the Home Care-Intellectual and Developmental Disabilities Frailty Index (HC-IDD Frailty Index), developed for use in home care users with IDD, to a basic list of predictors (age, sex, rural status, and the Johns Hopkins Frailty Marker) increases the ability to predict admission to long-term care or death within one year.

Patterns of mortality among adults with intellectual and developmental disabilities in Ontario.

Objectives: To determine recent mortality rates among Ontarian adults with intellectual and developmental disabilities (IDDs) and investigate changes over time in contrast to the general population. To determine the most commonly reported underlying causes of death and explore related coding practices.

Methods: Using linked health administrative data, four cohorts of adults with IDD aged 25-99 living in Ontario were followed for 1 year (one cohort for each year between 2011 and 2014).

The Prognostic Value of PIK3CA Copy Number Gain in Penile Cancer.

Objective: To determine whether phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha (PIK3CA) copy number gain in penile cancer has prognostic value and association with histopathological parameters, human papillomavirus (HPV), and clinical outcome.

Methods: PIK3CA copy number status was assessed with fluorescence in situ hybridization in tissue microarrays generated from archival paraffin embedded blocks of 199 patients with primary penile squamous cell carcinoma (PSCC). HPV DNA was detected with INNO-LiPA assay.

PIK3CA copy number aberration and activation of the PI3K-AKT-mTOR pathway in varied disease states of penile cancer.

Background: Therapeutic targeting of the PI3K-AKT-mTOR pathway may benefit patients with advanced penile squamous cell carcinoma (PSCC).

Objectives: To determine the prevalence of PIK3CA copy number gain and correlate this with the activity status of PI3K-AKT-mTOR pathway in pre-malignant penile intraepithelial neoplasia (PeIN) and invasive PSCC.

Materials And Methods: Archival tissue blocks were obtained from 58 PeIN and 244 primary PSCC patients treated at St George's Hospital.

Analysis of the PI3K-AKT-mTOR pathway in penile cancer: evaluation of a therapeutically targetable pathway.

Objectives: To determine whether phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha (PIK3CA) copy number gain is common and could prove a useful marker for the activation status of the PI3K-AKT-mTOR pathway in penile squamous cell carcinoma (PSCC).

Methods: Fresh frozen tissue and archival blocks were collected from 24 PSCC patients with 15 matched normal penile epithelium (NPE) tissue from St George's Hospital. PIK3CA mutational and copy number status (CNS) was assessed via Sanger sequencing and fluorescence hybridisation, respectively.

Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer.

Prostate cancer is the most common cancer among western men, with a significant mortality and morbidity reported for advanced metastatic disease. Current understanding of metastatic disease is limited due to difficulty of sampling as prostate cancer mainly metastasizes to bone. By analysing prostate cancer bone metastases using high density microarrays, we found a common genomic copy number loss at 6q16.

The Novel Association of Circulating Tumor Cells and Circulating Megakaryocytes with Prostate Cancer Prognosis.

To develop an approach for the investigation of different subtypes of circulating tumor cells (CTC) and other cells to evaluate their potential prognostic value of prostate cancer. Malignancy of CTCs undergoing epithelial-to-mesenchymal transition (EMT) was confirmed by repeated FISH. Subgroups of CTCs in 81 patients with prostate cancer (43 castration resistant and 38 untreated localized) were correlated to disease aggressiveness parameters.

NKAIN2 functions as a novel tumor suppressor in prostate cancer.

Recurrent chromosome breakpoints at 6q22.31, leading to truncation and potential loss-of-function of the NKAIN2 gene, in Chinese prostate cancer patients were previously identified. In this study we investigated genomic, methylation and expression changes of NKAIN2 in a large number of prostate cancer samples and determined its functional role in prostate cancer cells.

DNA Copy Number Aberrations, and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver Genes.

Penile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and clinico-pathological features. We sought to determine the spectrum of gene copy number aberrations in a large series of PSCCs and to define their correlations with human papillomavirus, histopathological subtype, and tumor grade, stage and lymph node status.

Involvement of different mechanisms for the association of CAG repeat length polymorphism in androgen receptor gene with prostate cancer.

While androgen and androgen receptor (AR) activity have been strongly implicated in prostate cancer development and therapy, the influence of the CAG repeat, which is found within the first exon of the AR gene, on prostate carcinogenesis is still unclear. We investigated the differences in the length of the CAG repeat between prostate cancer patients and controls in the Chinese population as well as between TMPRSS2:ERG fusion positive and negative samples. A general association between prostate cancer and either longer or shorter AR CAG repeat length was not observed in the Chinese population.

Chinese and Western prostate cancers show alternate pathogenetic pathways in association with ERG status.

We have previously reported genetic differences between Western and Chinese prostate cancers, including different frequencies of ERG rearrangements. We investigated further ERG expression and rearrangements in prostate cancers and high-grade prostatic intraepithelial neoplasia (HGPIN) from the UK and China to determine differences between these two populations by tissue microarray based immunohistochemistry and fluorescence in situ hybridization. In keeping with our previous observation, that ERG was rearranged at a higher frequency in UK prostate cancer samples (38%, 58/155) than Chinese ones (8%, 7/93), ERG rearrangements were also found in 21% (4/19) and 0% (0/19) foci of HGPIN in UK and Chinese samples respectively.

Identification of frequent BRAF copy number gain and alterations of RAF genes in Chinese prostate cancer.

We recently found that TMPRSS2:ERG fusion genes and PTEN loss, which are common in Western prostate cancers are infrequent in Chinese cases. As previous studies indicated a higher frequency of RAS and BRAF mutation rates in Eastern Asian than in Western prostate cancers and fusion genes involving the RAF family genes BRAF and RAF1 were recently identified in prostate cancer in the American population, we investigated BRAF and RAF1 alterations in Chinese prostate cancer. Using fluorescence in situ hybridization, we found that BRAF was truncated in five of 200 informative Chinese cases (2.

Neuroendocrine differentiation does not have independent prognostic value in conservatively treated prostate cancer.

In vitro studies have implicated neuroendocrine differentiation in the development of hormone resistant prostate cancer following administration of androgen blockers. Studies on clinical material are equivocal. We wished to understand the significance of neuroendocrine differentiation in our large and well-characterised cohort of clinically localised prostate cancer, treated conservatively.

The prognostic value of Ki-67 expression in penile squamous cell carcinoma.

Aims: To determine whether Ki-67 immunoexpression in penile squamous cell carcinoma (PSCC) has a prognostic value and correlates with lymph node metastasis, human papillomavirus (HPV) infection and patient survival.

Methods: 148 formalin-fixed paraffin-embedded PSCC samples were tissue-microarrayed, including 97 usual-type SCCs, 17 basaloid, 15 pure verrucous carcinomas, 2 warty and 17 mixed-type tumours. All samples were immunostained for Ki-67 protein.

High-resolution genome-wide copy-number analysis suggests a monoclonal origin of multifocal prostate cancer.

Many human cancers present as multifocal lesions. Understanding the clonal origin of multifocal cancers is of both etiological and clinical importance. The molecular basis of multifocal prostate cancer has previously been explored using a limited number of isolated markers and, although independent origin is widely believed, the clonal origin of multifocal prostate cancer is still debatable.

Number of microparticles generated during acute myocardial infarction and stable angina correlates with platelet activation.

Background And Aims: Elevated levels of circulating microparticles (MPs) have been reported in patients with acute myocardial infarction (AMI) and coronary artery disease. Platelet activation and inflammation have been recognized during AMI and stable angina (SA). We hypothesize that the origin and count of MPs in AMI and SA patients are related to markers of inflammation and platelet activation.