Addressing the false positive MRI phenotype in prostate cancer diagnosis and management

Multiparametric magnetic resonance imaging (mpMRI) is set to dominate the diagnosis and active surveillance of prostate cancer. However, false positive MRIs confound clinical decision-making and prompt unwarranted biopsies that carry morbidity risks. This is a significant issue: NICE currently recommends pre-biopsy MRI in men with suspected prostate cancer and, as 80,000 patients undergo biopsy every year in England and Wales, between 12,600 to 17,300 are expected to be biopsy-negative. Furthermore, MRI in active surveillance (AS) is strongly recommended by NICE for risk stratification at baseline and for the detection of oncological progression. However, MRI-based AS is new and it is still unknown when observed dynamic MRI changes reflect true transition to clinically significant disease. Recognising this on imaging is important for optimising clinical decisions and reducing the overall number of biopsies during AS. In this thesis it will be shown that MRI lesions seen in biopsy-naïve individuals with clinically significant cancer are larger, more conspicuous and more diffusion-restricted compared to phenotypes seen in men without significant disease. Furthermore, in men with indeterminate MRI phenotypes, PSA density and index lesion ADC predict the presence of significant cancer through a logistic regression model (mean cross-validated AUC: 0.77 [95% CI: 0.67–0.87]) and could help men avoid unnecessary biopsies. It is also shown that false positive MRI phenotypes in such men arise in prostatic regions with increased overall cellularity and expanded epithelium, while assuming either focal or diffuse patterns. In addition, it is demonstrated that MRI-based AS can be safely used to monitor men with insignificant disease, as approximately 84.7% (95% CI: 82.0–87.6) and 71.8% (95% CI: 68.2–75.6) of patients remain on AS at 3 and 5 years (with those with MRI-visible disease at baseline exiting earlier). Finally, it will be shown that progressing MRI lesions during imaging-based AS have two distinct histological phenotypes: one characterised by increased overall cellularity and expansion of epithelial areas (typically seen with transition to higher grade cancer) and another by moderate, standalone stromal hyperplasia seen in cases of pathological stability, not ideally requiring biopsy. This finding could lead to the development of radiological metrics that distinguish the two progression types and spare men from unnecessary biopsies in AS contexts

Small-scale intraspecific life history variation in herbivorous spider mites (Tetranychus pacificus) is associated with host plant cultivar.

Life history variation is a general feature of arthropod systems, but is rarely included in models of field or laboratory data. Most studies assume that local processes occur identically across individuals, ignoring any genetic or phenotypic variation in life history traits. In this study, we tested whether field populations of Pacific spider mites (Tetranychus pacificus) on grapevines (Vitis vinifera) display significant intraspecific life history variation associated with host plant cultivar. To address this question we collected individuals from sympatric vineyard populations where either Zinfandel or Chardonnay were grown. We then conducted a "common garden experiment" of mites on bean plants (Phaseolus lunatus) in the laboratory. Assay populations were sampled non-destructively with digital photography to quantify development times, survival, and reproductive rates. Two classes of models were fit to the data: standard generalized linear mixed models and a time-to-event model, common in survival analysis, that allowed for interval-censored data and hierarchical random effects. We found a significant effect of cultivar on development time in both GLMM and time-to-event analyses, a slight cultivar effect on juvenile survival, and no effect on reproductive rate. There were shorter development times and a trend towards higher juvenile survival in populations from Zinfandel vineyards compared to those from Chardonnay vineyards. Lines of the same species, originating from field populations on different host plant cultivars, expressed different development times and slightly different survival rates when reared on a common host plant in a common environment

Course-Prerequisite Networks for Analyzing and Understanding Academic Curricula

Understanding a complex system of relationships between courses is of great importance for the university's educational mission. This paper is dedicated to the study of course-prerequisite networks that model interactions between courses, represent the flow of knowledge in academic curricula, and serve as a key tool for visualizing, analyzing, and optimizing complex curricula. We show how course-prerequisite networks can be used by students, faculty, and administrators for detecting important courses, improving existing and creating new courses, navigating complex curricula, allocating teaching resources, increasing interdisciplinary interactions between departments, revamping curricula, and enhancing the overall students' learning experience. The proposed methodology is illustrated with a network of courses taught at the California Institute of Technology.Comment: 24 pages, 20 figures, 10 Table

A Case of Persistent Foot Pain in a Neurofibromatosis Type I Patient

Introduction. This is the case of a young male patient who presented to his family physician with atypical left foot pain, which was extremely resistant to analgesia and caused significant disability. Despite extensive investigations, the cause of his pain was not identified until 18 months after his initial symptoms, when the official diagnosis of malignant peripheral nerve sheath tumour (MPNST) was made. Detailed review of the patient's past history established the diagnosis of type I neurofibromatosis (NF-1), previously undetected. Discussion. NF-1 is an autosomal dominant genetic disorder caused by loss of function mutations of the NF1 gene in chromosome 17. Patients with this condition are at increased risk for developing MPNSTs which, however, are treatable only in early stages. Conclusion. Although monitoring NF-1 patients for the development of MPNSTs is common practice, the index of clinical suspicion in patients without an established NF-1 diagnosis is low. Any atypical pain in young adults should raise the possibility of this malignancy, and this case illustrates the fact that MPNSTs can be the first manifestation of NF-1 in patients previously undiagnosed with the disease

Social-Psychological Profiles of Early Adolescents Involved in Bullying Activities

Abstract: The purpose of the present study was to examine the differences existing between sub-groups of early adolescents involved in bullying activities at school. Specifically, the study aimed at comparing three identified groups (bullies, passive victims and aggressive victims or bully-victims) as well as uninvolved students in terms of a number of indicators of psycho-social adjustment; namely, empathy, impulsivity, hyperactivity, emotional and behavioral problems and pro-social skills. A representative sample of 454 Greek Cypriot students (mean age of 13.4) was selected from seven different public high schools. The participants completed a revised version of the Bullying and Victimization Questionnaire and based on their scores they were classified into one of four, mutually exclusive categories, those of bullies, victims, aggressive victims, and uninvolved. These groups were then compared regarding their mean scores on the Basic Empathy Scale, the Strengths and Difficulties Questionnaire, and the Urgency Subscale. Multiple post-hoc comparisons revealed that the aggressive victims group had the most problematic psycho-social profile. Specifically, aggressive victims were significantly more impulsive, less affectively empathic, and had lower prosocial skills, more behavioural problems and more hyperactivity. The results of the present study show that children and adolescents diagnosed as aggressive victims are at higher risk in a number of psychopathological characteristics that endanger typical development

Sensor Array Signal Processing via Eigenanalysis of Matrix Pencils Composed of Data Derived from Translationally Invariant Subarrays

An algorithm is developed for estimating characteristic parameters associated with a scene of radiating sources given the data derived from a pair of translationally invariant arrays, the X and Y arrays, which are displaced relative to one another. The algorithm is referred to as PR O—E SPRIT and is predicated on invoking two recent mathematical developments: (1) the SVD based solution to the Procrustes problem of optimally approximating an invariant subspace rotation and (2) the Total Least Squares method for perturbing each of the two estimates of a common subspace in a minimal fashion until the two perturbed spaces are the same. For uniform linear array scenarios, the use of forward-backward averaging (FBAVG) in conjunction with PR O—E S PR IT is shown to effect a substantial reduction in the computational burden, a significant improvement in performance, a simple scheme for estimating the number of sources and source decorrelation. These gains may be attributed to FBAVG’s judicious exploitation of the diagonal invariance operator relating the Direction of Arrival matrix of the Y array to that associated with the X array. Similar gains may be achieved in the case where the X and Y arrays are either not linear or not uniformly spaced through the use of pseudo-forward-backward averaging (PFBAVG). However, the use of PFBAVG does not effect source decorrelation and reduces the maximum number of resolvable sources by a factor of two. Simulation studies and the results of applying PR O—E S PR IT to real data demonstrate the excellent performance of the method

Scheduling Real-Time Jobs in Distributed Systems - Simulation and Performance Analysis

Proceedings of: First International Workshop on Sustainable Ultrascale Computing Systems (NESUS 2014). Porto (Portugal), August 27-28, 2014.One of the major challenges in ultrascale systems is the effective scheduling of complex jobs within strict timing constraints. The distributed and heterogeneous system resources constitute another critical issue that must be addressed by the employed scheduling strategy. In this paper, we investigate by simulation the performance of various policies for the scheduling of real-time directed acyclic graphs in a heterogeneous distributed environment. We apply bin packing techniques during the processor selection phase of the scheduling process, in order to utilize schedule gaps and thus enhance existing list scheduling methods. The simulation results show that the proposed policies outperform all of the other examined algorithms.The work presented in this paper has been partially supported by EU under the COST program Action IC1305, “Network for Sustainable Ultrascale Computing (NESUS)”

Magnetic Resonance Imaging–guided Active Surveillance of Prostate Cancer: Time to Say Goodbye to Protocol-based Biopsies

Traditional protocols for active surveillance (AS) are commonly based on digital rectal examination, prostate-specific antigen (PSA), and standard transrectal biopsy, meaning that initial classification errors and inaccurate lesion monitoring can occur. Protocol-based biopsies are performed to assess changes in cancer grade and extent at prespecified intervals, but this approach represents a barrier to AS adherence and tolerability. There is evidence to support the use of magnetic resonance imaging (MRI) during AS, as this technique (associated with favourable PSA kinetics) offers an opportunity to follow patients on AS without the need for routine, protocol-based biopsies in the absence of signs of radiological progression provided that image quality, interpretation, and reporting of serial imaging are of the highest standards. Patient summary: In this report we looked at the role of magnetic resonance imaging (MRI) scans in avoiding unnecessary prostate biopsies for patients being monitored for low- or intermediate-risk prostate cancer. We conclude that patients on active surveillance can be monitored with MRI scans over time and that biopsies could be used only when there are changes on MRI or a rising prostate-specific antigen (PSA) not explained by an increase in prostate size

Workplace Bullying and Victimization: A Mixed Method Approach

Purpose: The main scope of the survey was to examine how school bullying and victimization experiences affect workplace bullying and victimization, as also the role of the personality traits and workplace environment to this relation. It also aimed to investigate the consequences on mental health of employees who are targets of workplace victimization, as well as the reaction mechanisms of employees against bullying. Method: 302 employees from four private companies in Cyprus completed the Organizational Culture Assessment Instrument, Five Factor Personality Inventory Questionnaire, Retrospective Bullying Questionnaire, Post-traumatic Embitterment Disorder Self-Rating, Negative Acts Questionnaire – Revised, and a list of coping skills, in one-time phase. Results: Based on the results, school victimization experiences and neuroticism, influenced the occurrence of workplace victimization, as also workplace climate affected the above relationship. Workplace climate, workplace victimization and neuroticism, found to be related with the development of Post-Traumatic Embitterment Disorder. In addition, neuroticism and workplace victimization mediated by employees’ coping skills