Identifying prognostic structural features in tissue sections of colon cancer patients using point pattern analysis

Diagnosis and prognosis of cancer is informed by the architecture inherent in cancer patient tissue sections. This architecture is typically identified by pathologists, yet advances in computational image analysis facilitate quantitative assessment of this structure. In this article we develop a spatial point process approach in order to describe patterns in cell distribution within tissue samples taken from colorectal cancer (CRC) patients. In particular, our approach is centered on the Palm intensity function. This leads to taking an approximate-likelihood technique in fitting point processes models. We consider two Neyman-Scott point processes and a void process, fitting these point process models to the CRC patient data. We find that the parameter estimates of these models may be used to quantify the spatial arrangement of cells. Importantly, we observe characteristic differences in the spatial arrangement of cells between patients who died from CRC and those alive at follow-up

Functional brain imaging studies of youth depression: A systematic review

AbstractBackgroundThere is growing interest in understanding the neurobiology of major depressive disorder (MDD) in youth, particularly in the context of neuroimaging studies. This systematic review provides a timely comprehensive account of the available functional magnetic resonance imaging (fMRI) literature in youth MDD.MethodsA literature search was conducted using PubMED, PsycINFO and Science Direct databases, to identify fMRI studies in younger and older youth with MDD, spanning 13–18 and 19–25years of age, respectively.ResultsTwenty-eight studies focusing on 5 functional imaging domains were identified, namely emotion processing, cognitive control, affective cognition, reward processing and resting-state functional connectivity. Elevated activity in “extended medial network” regions including the anterior cingulate, ventromedial and orbitofrontal cortices, as well as the amygdala was most consistently implicated across these five domains. For the most part, findings in younger adolescents did not differ from those in older youth; however a general comparison of findings in both groups compared to adults indicated differences in the domains of cognitive control and affective cognition.ConclusionsYouth MDD is characterized by abnormal activations in ventromedial frontal regions, the anterior cingulate and amygdala, which are broadly consistent with the implicated role of medial network regions in the pathophysiology of depression. Future longitudinal studies examining the effects of neurodevelopmental changes and pubertal maturation on brain systems implicated in youth MDD will provide a more comprehensive neurobiological model of youth depression

Modulation of Brain Resting-State Networks by Sad Mood Induction

BACKGROUND: There is growing interest in the nature of slow variations of the blood oxygen level-dependent (BOLD) signal observed in functional MRI resting-state studies. In humans, these slow BOLD variations are thought to reflect an underlying or intrinsic form of brain functional connectivity in discrete neuroanatomical systems. While these 'resting-state networks' may be relatively enduring phenomena, other evidence suggest that dynamic changes in their functional connectivity may also emerge depending on the brain state of subjects during scanning. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we examined healthy subjects (n = 24) with a mood induction paradigm during two continuous fMRI recordings to assess the effects of a change in self-generated mood state (neutral to sad) on the functional connectivity of these resting-state networks (n = 24). Using independent component analysis, we identified five networks that were common to both experimental states, each showing dominant signal fluctuations in the very low frequency domain (approximately 0.04 Hz). Between the two states, we observed apparent increases and decreases in the overall functional connectivity of these networks. Primary findings included increased connectivity strength of a paralimbic network involving the dorsal anterior cingulate and anterior insula cortices with subjects' increasing sadness and decreased functional connectivity of the 'default mode network'. CONCLUSIONS/SIGNIFICANCE: These findings support recent studies that suggest the functional connectivity of certain resting-state networks may, in part, reflect a dynamic image of the current brain state. In our study, this was linked to changes in subjective mood

The Neural Correlates of Problem States: Testing fMRI Predictions of a Computational Model of Multitasking

Background: It has been shown that people can only maintain one problem state, or intermediate mental representation, at a time. When more than one problem state is required, for example in multitasking, performance decreases considerably. This effect has been explained in terms of a problem state bottleneck. Methodology: In the current study we use the complimentary methodologies of computational cognitive modeling and neuroimaging to investigate the neural correlates of this problem state bottleneck. In particular, an existing computational cognitive model was used to generate a priori fMRI predictions for a multitasking experiment in which the problem state bottleneck plays a major role. Hemodynamic responses were predicted for five brain regions, corresponding to five cognitive resources in the model. Most importantly, we predicted the intraparietal sulcus to show a strong effect of the problem state manipulations. Conclusions: Some of the predictions were confirmed by a subsequent fMRI experiment, while others were not matched by the data. The experiment supported the hypothesis that the problem state bottleneck is a plausible cause of th

On Multiphase-Linear Ranking Functions

Multiphase ranking functions ($\mathit{M{\Phi}RFs}$) were proposed as a means to prove the termination of a loop in which the computation progresses through a number of "phases", and the progress of each phase is described by a different linear ranking function. Our work provides new insights regarding such functions for loops described by a conjunction of linear constraints (single-path loops). We provide a complete polynomial-time solution to the problem of existence and of synthesis of $\mathit{M{\Phi}RF}$ of bounded depth (number of phases), when variables range over rational or real numbers; a complete solution for the (harder) case that variables are integer, with a matching lower-bound proof, showing that the problem is coNP-complete; and a new theorem which bounds the number of iterations for loops with $\mathit{M{\Phi}RFs}$. Surprisingly, the bound is linear, even when the variables involved change in non-linear way. We also consider a type of lexicographic ranking functions, $\mathit{LLRFs}$, more expressive than types of lexicographic functions for which complete solutions have been given so far. We prove that for the above type of loops, lexicographic functions can be reduced to $\mathit{M{\Phi}RFs}$, and thus the questions of complexity of detection and synthesis, and of resulting iteration bounds, are also answered for this class.Comment: typos correcte

Non-destructive characterization of thin layer resonant tunnelling diodes

We present an advanced nondestructive characterization scheme for high current density AlAs/InGaAs resonant tunneling diodes pseudomorphically grown on InP substrates. We show how low-temperature photoluminescence spectroscopy (LT-PL) and high-resolution X-ray diffractometry (HR-XRD) are complementary techniques to increase the confidence of the characterized structure. The lattice-matched InGaAs is characterized and found to be of high quality. We discuss the inclusion of an undoped “copy” well (C-well) in terms of enhancements to HR-XRD and LT-PL characterization and quantify the improved precision in determining the structure. As a consequence of this enhanced precision in the determination of physical structure, the AlAs barriers and quantum well (QW) system are found to contain nonideal material interfaces. Their roughness is characterized in terms of the full width to half-maximum of the split LT-PL emission peaks, revealing a ±1 atomic sheet variance to the QW width. We show how barrier asymmetry can be detected through fitting of both optical spectra and HR-XRD rocking curves

Bringing Authoring Tools for Intelligent Tutoring Systems and Serious Games Closer Together: Integrating GIFT with the Unity Game Engine

In an effort to bring intelligent tutoring system (ITS) authoring tools closer to content authoring tools, the authors are working to integrate GIFT with the Unity game engine and editor. The paper begins by describing challenges faced by modern intelligent tutors and the motivation behind the integration effort, with special consideration given to how this work will better meet the needs of future serious games. The next three sections expand on these major hurdles more thoroughly, followed by proposed design enhancements that would allow GIFT to overcome these issues. Finally, an overview is given of the authors’ current progress towards implementing the proposed design. The key contribution of this work is an abstraction of the interface between intelligent tutoring systems and serious games, thus enabling ITS authors to implement more complex training behaviors

Task-Related Deactivation and Functional Connectivity of the Subgenual Cingulate Cortex in Major Depressive Disorder

Background: Major depressive disorder is associated with functional alterations in activity and resting-state connectivity of the extended medial frontal network. In this study we aimed to examine how task-related medial network activity and connectivity were affected in depression. Methods: 18 patients with major depressive disorder, aged 15- to 24-years-old, were matched with 19 healthy control participants. We characterized task-related activations and deactivations while participants engaged with an executive-control task (the multi-source interference task, MSIT). We used a psycho-physiological interactions approach to examine functional connectivity changes with subgenual anterior cingulate cortex. Voxel-wise statistical maps for each analysis were compared between the patient and control groups. Results: There were no differences between groups in their behavioral performances on the MSIT task, and nor in patterns of activation and deactivation. Assessment of functional connectivity with the subgenual cingulate showed that depressed patients did not demonstrate the same reduction in functional connectivity with the ventral striatum during task performance, but that they showed greater reduction in functional connectivity with adjacent ventromedial frontal cortex. The magnitude of this latter connectivity change predicted the relative activation of task-relevant executive-control regions in depressed patients. Conclusion: The study reinforces the importance of the subgenual cingulate cortex for depression, and demonstrates how dysfunctional connectivity with ventral brain regions might influence executive–attentional processes

Distinct etiological influences on obsessive-compulsive symptoms dimensions: A multivariate twin study

Background Obsessive-compulsive disorder (OCD) is characterized by five major dimensions, including contamination/washing, harm/checking, symmetry/ordering, hoarding, and forbidden thoughts. How these dimensions may relate etiologically to the symptoms of other obsessive-compulsive related disorders (OCRDs) and anxiety disorders (ADs) is not well known. The aim of this study was to examine the genetic and environmental overlap between each major obsessive-compulsive dimension with the symptoms of other OCRDs and ADs. MethodsTwo thousand four hundred ninety-five twins of both sexes, aged between 18 and 45 years, were recruited from the Australian Twin Registry. Measures used scores on four dimensions (obsessing (forbidden thoughts), washing, checking, and ordering) of the Obsessive-Compulsive Inventory-Revised, Dysmorphic Concerns Questionnaire, Hoarding Rating Scale, Anxiety Sensitivity Index, Social Phobia Inventory, and Stress subscale of the Depression, Anxiety, and Stress Scale. Multivariate twin modeling methods using continuous and categorized variables were performed, also controlling for age and gender. ResultsOur findings suggested that forbidden thoughts and washing demonstrated the strongest genetic overlap with other AD symptoms, while ordering was genetically related to OCRD symptoms. Common genetic influences on checking symptoms were best estimated when modeling OCRDs together with AD symptoms. Common environmental factors of ordering and checking were shared with AD symptoms. ConclusionsImportant shared genetic and environmental risk factors exist between OCD, OCRDs, and ADs, but which vary alongside the expression of its major dimension